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# Enhanced Fusion-Evaporation Cross Sections in Neutron-Rich 132Sn on 64Ni

## Abstract

Evaporation residue cross sections have been measured with neutron-rich radioactive 132Sn beams on 64Ni in the vicinity of the Coulomb barrier. The average beam intensity was $`2\times 10^4`$ particles per second and the smallest cross section measured was less than 5 mb. Large subbarrier fusion enhancement was observed. Coupled-channels calculations taking into account inelastic excitation and neutron transfer underpredict the measured cross sections below the barrier.

The interaction of two colliding nuclei consists of an attractive nuclear potential and a repulsive Coulomb potential. This creates a Coulomb barrier which the system has to overcome in order to fuse. At energies below the barrier, fusion occurs by quantum tunneling. Subbarrier fusion cross sections for heavy ions are often found enhanced over the one-dimensional barrier penetration model (BPM) prediction. The enhancement can be explained in most cases by the coupling of the relative motion and the nuclear structure degrees of freedom of the participating nucleibe88 . It has been suggested that the fusion yield would be further enhanced when the reaction is induced by unstable neutron-rich nucleita92 ; hu91 ; da92 . This is attributed to the large N/Z ratio of these nuclei reducing the barrier height and the presence of a large number of nucleon transfer channels which can serve as doorways to fusionki94 . The compound nucleus can be formed at lower excitation energies and with a smaller fissility and, therefore, a higher survival probability for the evaporation residues (ERs). Subbarrier fusion can be used in experiments to produce superheavy elements. It is beneficial to produce them near the neutron shell closure to increase their lifetimes. If neutron-rich radioactive beams are used in such experiments, heavy ions as projectiles are required, since it is not possible to find a suitable target with light ion beams.

The experimental search for fusion enhancement in heavy ion reactions has been pursued at several laboratories using neutron-rich radioactive beams. The measurements of 38S+181Tazy97  and 29,31Al+197Ausi01  found only the enhancement expected from the lowering of the barrier height caused by the larger radii of the neutron-rich nuclei compared to the stable 32S and 27Al, respectively. This paper reports the first reaction study using accelerated unstable neutron-rich 132Sn beams to measure fusion-evaporation cross sections. The doubly magic 132Sn (Z=50, N=82) has eight extra neutrons compared to the heaviest stable Sn isotope, 124Sn. The N/Z ratio of 132Sn (1.64) is larger than that of 48Ca (1.4) and 208Pb (1.54) which are closed shell nuclei commonly used to produce heavy elementsho00 . The target, 64Ni, is semi-magic (Z=28) and is the most neutron-rich stable isotope of nickel. The compound nucleus formed in this experiment, 196Pt, lies in the valley of $`\beta `$-stability. It has excitation energies greater than 30 MeV and can decay by particle evaporation or fission.

The experiment was carried out at the Holifield Radioactive Ion Beam Facility (HRIBF) at Oak Ridge National Laboratory. The isotope separator on-line technique was used to produce radioactive 132Sn. A uranium carbide target was bombarded by a 42 MeV proton beam accelerated by the Oak Ridge isochronous cyclotron. Isobaric contaminants at A=132 were suppressed by extracting molecular SnS+ from the ion source and subsequently breaking it up in the charge exchange cell where the SnS+ was converted to Sn-st03  for injecting into the 25 MV tandem post accelerator. The 132Sn ions were accelerated to six energies (453, 475, 489, 504, 536, and 560 MeV) and delivered to the target. The beam intensity was measured by passing it through a 10 $`\mu `$g/cm2 carbon foil and detecting the secondary electrons in a microchannel plate (MCP) detector. Three of these MCP systems were used in this experiment for monitoring the beam and providing timing signals. The average beam intensity was 2$`\times 10^4`$ particles per second (pps) with a maximum near 3$`\times 10^4`$ pps. The purity of the 132Sn beam was checked by measuring the energy loss in an ionization chamber (IC). A 132Te beam was used to calibrate the energy loss spectrum. It was determined that the impurity was less than 2% and that all measurable impurities had a higher atomic number (Z) than Sn. This impurity has negligible effect on the measurement because the higher Coulomb barrier suppresses the fusion of the contaminants with the target. A 124Sn beam was used as a guide beam to set up the accelerator and beam line optics. At the target position, the beam was focused to a spot 1.0 mm horizontally and 2.5 mm vertically. The shape of the guide beam was recorded by an electronic phosphorsh98  consisting of an aluminized mylar foil and a position sensitive microchannel plate detector located 74 cm in front of the target. This beam was also used for testing the detector system. The 132Sn beam was then tuned by scaling the optical elements and comparing the beam shape with that of the guide beam using the electronic phosphor.

The ERs were detected along with beam particles by a timing detector and an IC located 16.9 cm from the target at 0. They were identified by their time-of-flight and energy loss in the IC. The acceptance of the timing detector was a 2.54 cm diameter circle and the detection efficiency was approximately 100% for these heavy ions. In the time-of-flight measurement, the coincidence between two timing detectors placed 119 and 315 cm upstream from the target provided the timing references. The data acquisition was triggered by the scaled down beam singles or the ER-beam particle coincidences. With this triggering scheme an overall deadtime of less than 5% was achieved. The IC was filled with CF4 gas. The pressure was adjusted between 50 and 60 Torr to optimize the separation of ERs from the beam. A detailed description of the experimental apparatus will be published elsewheresh03 . Figure 1 shows the histogram of the energy loss in the first two segments of the IC for a beam energy of 536 MeV. Although there is some signal pile-up introduced by directly injecting the beam into the detector, it is clear that the ERs are still well separated from the beam. With this setup, measurement of ER cross sections less than 5 mb can be achieved.

The cross section was obtained by integrating the ER yield and summing the beam particles in the IC. Because of the low intensity of radioactive beams, the measurement was performed with a thick target, 1 mg/cm2 self-supporting highly enriched (99.81%) 64Ni foil. The target thickness was determined by measuring the energy loss of $`\alpha `$ particles emitted from a 244Cm source and a 536 MeV 132Sn beam passing through the target, and by measuring the weight and area of the target. The energy loss of 132Sn projectiles in the target was approximately 40 MeV. At energies below the Coulomb barrier, the excitation function falls off exponentially. For this reason, the measured cross section ($`\sigma _{meas}`$) is sensitive predominantly to the front portion of the target and is actually a weighted average of the cross section over the range of energy loss in the target, from the energy of the beam entering the target ($`E_{in}`$) to that exiting the target ($`E_{out}`$), namely,

$$\sigma _{meas}=\frac{_{E_{in}}^{E_{out}}\sigma (E)𝑑E}{_{E_{in}}^{E_{out}}𝑑E}.$$
(1)
To determine the effective reaction energy, the cross section was parameterized as an exponential function, $`\sigma (E)=N\mathrm{exp}(\alpha E)`$, where $`N`$ is a normalization factor and $`\alpha `$ is a slope parameter. By solving the integral equation (1) for two adjacent data points in the excitation function, $`N`$ and $`\alpha `$ were obtained. Subsequently, the effective energy is deduced by inverting the exponential function, namely, $`E=ln(\sigma _{meas}/N)/\alpha `$ .

Since this experiment was performed in inverse kinematics (a heavy projectile on a light target) the ERs were very forward focused. However, the shape of the beam spot was not symmetric. Moreover, one of the disadvantages of using a thick target is the multiple scattering which results in broadening the angular distribution. Monte Carlo simulations were used to estimate the efficiency of the apparatus. The angular distribution of ERs was generated by the statistical model code pacega80  and the width of the distribution of multiple scattering angles was predicted by Ref ma67 . The simulations show that the efficiency of the apparatus changes from $`95\pm 1`$% for the lowest beam energy to $`98\pm 1`$% for the highest energy.

Figure 2 presents the fusion-evaporation excitation function of 132Sn+64Ni measured in this work (solid circles) and that of 64Ni+124Sn measured by Freeman et al.fr83  (open triangle). The open circle is our measurement using the 124Sn guide beam which is consistent with the measurement in Ref. fr83 . The uncertainty in energy for our data is smaller than the size of the symbol in the figure. To compare the two excitation functions, the energy of 132Sn+64Ni is shifted by the difference between the fusion barriers for the two systems predicted by the Bass modelba74  ($`\mathrm{\Delta }V_B=1.93`$ MeV). The energy shifted excitation function of 132Sn+64Ni is shown by the solid curve in Fig. 2. It can be seen that at the highest energy the ER cross sections for 132Sn+64Ni are larger. This can be expected from the higher stability against fission for the neutron-rich compound nucleus. At energies below the barrier, the ER cross sections for 132Sn+64Ni are found much enhanced comparing to those of 64Ni+124Sn and a simple shift of the barrier height cannot explain the enhancement.

To compare the measured excitation function with fusion models, it is necessary to estimate fission yields in the reaction. Statistical model calculations were carried out using the code pace. The input parameters were determined by reproducing the ER and fission cross sections of 64Ni+124Sn in Ref. le86 . The following parameters were used: level density parameter $`a=A/8`$ MeV-1 where $`A`$ is the mass of the compound nucleus, ratio of the Fermi gas level density parameter at the saddle point to that of the ground state $`a_f/a_n=1`$, diffuseness of spin distribution $`d=4\mathrm{}`$, and Sierk’s fission barriersi86 . The calculations predict that fission is negligible for 132Sn+64Ni and 64Ni+124Sn at E$`{}_{\mathrm{c}.\mathrm{m}.}{}^{}160`$ MeV. Therefore, the following discussion will be restricted to the data points at E$`{}_{\mathrm{c}.\mathrm{m}.}{}^{}160`$ MeV where the ER cross sections are taken as fusion cross sections.

Large subbarrier fusion enhancement in 132Sn+64Ni can be seen when the excitation function is compared to a one-dimensional BPM shown by the dotted curve in the upper panel of Fig. 3. The nuclear potential was assumed to have a Woods-Saxon shape. The potential parameters were obtained by adjusting them to reproduce the fusion cross section of 64Ni+124Sn in Ref. le86  at high energies. They are: depth $`V_{}=76.6`$ MeV, radius parameter $`r_{}=1.2`$ fm, and diffuseness parameter $`a=0.65`$ fm.

It is well established that subbarrier fusion enhancement can be described by channel couplingsbe88 . The couplings result in splitting the single barrier into a distribution of barriers. The incident flux overcoming the low energy barriers gives rise to the enhanced fusion cross sectionsro91 ; da98 ; ba98 . Coupled-channels calculations were performed with the code ccfullha99  which takes into account the effects of nonlinear coupling to all orders. The calculations used the same nuclear potential as that for the BPM calculation. The dashed curves in Fig. 3 is the result of coupling to inelastic excitation (IE) of the projectile and target. Table 1 lists the states and parametersra87 ; sp89  for the calculations. As shown in the lower panel of Fig. 3, the calculation reproduces the 64Ni+124Sn cross sections fairly well at low energies. For 132Sn+64Ni, the calculation significantly underpredicts the subbarrier cross sections as shown in the upper panel of Fig. 3. The small effect of coupling to IE in 132Sn can be attributed to the high excitation energy of the 2+ excited state and the small reduced transition probability (B(E2)).

In 64Ni+124Sn, the two neutron transfer reaction is the only transfer channel which has a positive Q-value. Coupled-channels calculations including this channel with an empirically determined coupling constant of 0.25 MeV and IE are in good agreement with the fusion cross sections near and below the barrier, as can be seen by the solid curve in the lower panel of Fig. 3. It is noted that the code ccfull is suitable for reactions where multinucleon transfer is less important than IEha99  as is the case in 64Ni+124Sn. For the 132Sn-induced reaction, the Q-values are positive for transfer of two to six neutrons. This large number of neutron transfer channels with positive Q-values and the small effects of IE channel coupling suggest that multi-neutron transfer could play an important role in the observed fusion enhancement. Although ccfull is not expected to treat the coupling of multinucleon transfer accurately, exploratory calculations were carried out to provide preliminary estimate of the effects of coupling to these channels. Results of calculations including these transfer channels and IE are shown by the solid curve in the upper panel of Fig. 3. The calculation cannot account for the cross sections near and below the barrier, nevertheless, it illustrates qualitatively the enhancement of subbarrier fusion due to the coupling to multinucleon transfer. It would be interesting to study near-barrier fusion further using even more neutron-rich Sn isotopes. However, this will be a very challenging task because the present beam intensity for 134Sn at HRIBF is approximately 2000 pps and highly contaminated. On the other hand, HRIBF can provide other pure neutron-rich radioactive beams such as Br and I with reasonable intensities for further studies.

In the future, it is necessary to measure fission for 132Sn+64Ni in order to obtain the fusion cross sections and study the survival probability of the compound nucleus. In addition, it was found that the extra-push energysw81  is needed for compound nucleus formation in 64Ni on stable even Sn isotopes at high energiesle86  and the extra-push energy diminishes as the number of neutrons in Sn increases. The threshold for requiring the extra-push energy given in Ref. le86  is near the 132Sn+64Ni system. This can be investigated by measuring ER and fission cross sections at higher energies.

In summary, fusion-evaporation cross sections using neutron-rich 132Sn beams on a 64Ni target were measured at energies near the Coulomb barrier. At the highest energy the ER cross section is larger than that of 64Ni on stable 124Sn. This is expected since the extra neutrons increase the survival probability of the compound nucleus. However, measurements of both ER and fission cross sections at higher energies will illustrate this better. Large subbarrier fusion enhancement using neutron-rich radioactive heavy ion beams was observed in this experiment. The subbarrier enhancement cannot be explained by a simple shift of the barrier height, or by channel couplings to inelastic excitation channels. There are five neutron transfer channels which have large positive Q-values. These reaction channels may serve as doorways to fusion. Further experiments using neutron-rich radioactive beams would advance our understanding of the mechanism for the fusion enhancement, and provide valuable information for using such beams to produce superheavy elements at future radioactive beam facilities.

We wish to thank the HRIBF staff for providing excellent radioactive beams and technical support. We wish to thank S. Novotny for his help with the apparatus. Research at the Oak Ridge National Laboratory is supported by the U.S. Department of Energy under contract DE-AC05-00OR22725 with UT-Battelle, LLC. W.L. and D.P. are supported by the the U.S. Department of Energy under grant no. DE-FG06-97ER41026.


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# Dynamics of non-equilibrium membrane bud formation

## Abstract

The dynamical response of a lipid membrane to a local perturbation of its molecular symmetry is investigated theoretically. A density asymmetry between the two membrane leaflets is predominantly released by in-plane lipid diffusion or membrane curvature, depending upon the spatial extent of the perturbation. It may result in the formation of non-equilibrium structures (buds), for which a dynamical size selection is observed. A preferred size in the $`\mu m`$ range is predicted, as a signature of the crossover between membrane and solvent dominated dynamical membrane response.

The formation of small membrane structures (vesicles or tubules…) is required for most inter and intra cellular transports in biological cellsalberts . While important progress have been made in the identification of key membrane proteins, recent work have focused on the lipid molecules themselveslipidmodif1 . Of particular interest is the lipid translocation by specific enzymes (flippases), and the membrane morphological changes they triggerlipidtransloc2 ; lipidtransloc1 . From a physical point of view, the formation of a bud from a fluid membrane has mostly been considered as the result of phase separation in mixed membranesvesicle1 , or as a global shape transition of closed membranes due to geometric frustrationpurebud . The final membrane conformation then corresponds to a global equilibrium, and is not expected to strongly depend upon dynamicsbuddyn . Small invaginations of the plasma membrane of biological cells should however result from localized perturbations, rather than from global changes at the scale of the cell. This paper present a theory for the dynamics of relaxation of one such local perturbation; a local membrane asymmetry, created by a sudden flip of a number of lipid from one leaflet of the bilayer to the other. This situation is of fundamental interest, as it may result in the formation of non-equilibrium membrane structures. The model also seeks to mimic experiments where the local perturbation of a giant vesicle ($`100\mu m`$) by adsorption of DNA molecules results in the production of small dynamical vesicles ($`\mu `$m) with their membrane packed with adsorbed DNAagelDNA1 .

In the present theoretical analysis, it is shown that the local membrane perturbation introduced by lipid translocation (stretching of the depleted monolayer, and compression of the enriched one, Fig.1), may be released both by opposite monolayer flows, leading to a diffusion of the perturbation (Fig.1a) or by membrane curvature (Fig.1b). While the former mechanism potentially leads to a vanishingly small energy, the faster of the two processes will control the membrane relaxation. It is shown below that large-scale membrane curvature is hindered by bulk flow, while small scale-membrane curvature is slowed by membrane flow. The cross-over between these two regimes defines a critical dynamical lengthscale $`\lambda _D1\mu `$m in water and $`100`$nm in the more viscous inner cellular environment, at which the perturbation is optimally converted into transient membrane curvature, and fully formed membrane bud are most likely to be observed.

Lipid membranes are self-assembled fluid bilayers. Their equilibrium properties such as lipid density $`\varphi _0`$ and membrane thickness $`2d`$ ($`4`$nm), result from a balance of the hydrophobic attractions between the lipid tails by steric or electrostatic repulsionsseifert . Deviation from the optimal density costs an elastic energy (per monolayer, per unit area) $`K_s(\varphi \varphi _0)^2/(2\varphi _0^2)`$, with a large stretching modulus $`K_s25k_BT/nm^2`$evans  ($`k_BT`$ is the thermal energy). The membrane bending energy $`\kappa C^2/2`$ involves the local membrane curvature $`C`$ and a fairly small bending modulus $`\kappa 25k_BT`$. Noting the outer (+) and inner (-) monolayer densities (at the mid-plane) $`\psi _\pm `$ (with $`\varphi _\pm =\psi _\pm (1dC)`$), the membrane elastic energy is best expressed in terms of the local average dilation $`\overline{\rho }\frac{\psi _++\psi _{}}{2\psi _0}1`$ and the dilation difference between the monolayers $`\rho \frac{\psi _+\psi _{}}{2\psi _0}`$seifert :

$$_{elast}=𝑑S(K_s(\rho dC)^2+K_s\overline{\rho }^2+\frac{\kappa }{2}C^2)$$
(1)
Bending a symmetrical bilayer ($`\rho =0`$) involves a bending modulus $`\kappa +2K_sd^2200k_BT`$. It is reduced to $`\kappa `$ in fluid membranes since the monolayer densities can adjust to $`\rho =dC`$. The (small) “bending ratio” of these two quantities $`ϵ\kappa /(2K_sd^2)`$ will prove important later.

Here, we study the membrane response to the sudden establishment of a local concentration asymmetry: some fraction $`\rho _0`$ of lipid being flipped from the “down” to the “up” monolayer over an area $`S_0`$ (Fig.1). For simplicity the membrane bears no global surface tension, which is to say that $`\overline{\rho }=0`$ throughout. Lipid flow toward the stretched region of the “down” monolayer and away from the compressed region of the “up” monolayer, diffuse the perturbation over the membrane (Fig.1a). Concomitantly, the compression-extension creates a bending torque leading to membrane curvature (Fig.1b). Diffusion of the perturbation is limited by the sliding friction between monolayers, while membrane curvature is limited by membrane and solvent viscous dissipation.

Local balance between elastic and dissipative forces yields local equations for the evolution of the membrane shape. Such equations exist for small membrane deformationsseifert , but are hardly tractable for large deformations. In consequence, we take a simpler approach where the perturbed membrane (of area $`S(t)`$) is parameterized by a spherical cap of constant curvature $`C(t)`$ and constant dilation difference $`\rho (t)`$, connected to an unperturbed (flat - $`C=\rho =0`$) membrane, see Fig.1b. This approximation disregards the existence of a connecting neck between the bud and the flat membrane, the stability of which probably influences the scission of the bud by membrane fusionfusion . In this work, buds are simply assumed to detach beyond a critical value of the budding parameter (defined in Eq.(2)). In the biological context, it may correspond to a neck small enough for membrane proteins such as dynamin to pinch off the buddynamin .

Spontaneous lipid flip-flop between the two monolayers is very unlikely over the evolution time, which imposes the conservation of asymmetry $`S(t)\rho (t)=S_0\rho _0`$. The stretching stress in the perturbed region is released when $`C=\rho /d`$ (Eq.(1)). The membrane geometry is described by a budding parameter, equal to unity for closed buds:

$$0<B_d\frac{SC^2}{16\pi }<B_d^{(0)}$$
(2)
where $`B_d^{(0)}=S_0\rho _0^2/(16\pi d^2)`$ corresponds to a situation where the perturbation is entirely converted into curvature, without diffusion along the membrane. As we will see, $`B_d`$ is always much smaller than $`B_d^{(0)}`$. The optimal conversion of perturbation into curvature is observed for a particular dynamical lengthscale $`\sqrt{S_0}\lambda _D`$ (Eq.(9)).

Dynamical equations for the two independent variables $`S`$ and $`C`$ are obtained using a Lagrangian descriptiongoldstein , where elastic and dissipative “forces” are calculated from the variation of the elastic energy $`_{elast}[\{\rho ,C\}]`$, and the energy dissipated per unit time $`𝒫_{diss}`$:

$$\frac{_{elast}}{\{\rho ,C\}}+\frac{𝒫_{diss}}{\{d_t\rho ,d_tC\}}=0$$
(3)
Variation with $`\rho `$ accounts for the migration of lipid molecules under a gradient of chemical potential, and variation with $`C`$ describes the membrane deformation due to the bending torque.

The three sources of dissipation involve three constitutive parameters. The viscosities of the solvent $`\eta `$ ($`10^3`$N/m2 for water) and of the membrane $`\mu _m`$ ($`10^9`$N.s/m), couple to gradients of bulk and membrane velocity fields $`𝐯`$ into viscous shear stresses $`\sigma _{ij}=\eta \left(_jv_i+_iv_j\right)`$brenner . An interlayer friction parameter $`b_m`$ ($`10^8`$N.s/m3), couples to the velocity difference $`\delta v`$ between membrane the two monolayers in relative motionevans . Note that $`\mu _m`$ and $`b_m`$ are related to the membrane (3-dimensional) viscosity $`\eta _m`$ by the scaling relations $`\eta _m\mu _m/db_md`$, where the membrane viscosity is typically a thousand times the viscosity of water $`\eta _m1`$ N/m2dimova . The total dissipation is $`𝒫_{diss}=𝒫_{b_m}+𝒫_{\mu _m}+𝒫_\eta `$, with

$$𝒫_{b_m}=\frac{b_m}{2}𝑑S\delta v^2;𝒫_\eta =\frac{1}{2\eta }𝑑V\underset{ij}{}(\sigma _{ij})^2$$
(4)
The membrane viscous dissipation $`𝒫_{\mu _m}`$ is obtained by substituting $`\mu _m`$ to $`\eta `$ in $`𝒫_\eta `$ and integrating over the membrane surface instead of the volume.

The three contributions to the energy dissipation are calculated as follows (see fisher  for a related calculation). The bud volume $`V`$ and neck aperture $`L`$ satisfy $`V=\frac{S^2C}{8\pi }\left(1\frac{2}{3}B_d\right)`$, $`\pi L^2=S(1B_d)`$. The curvilinear, radial, and spherical coordinate systems defined Fig.2 are used to parameterize flows in the curved and flat part of the membrane, and in the bulk, respectively. The differential monolayer velocity $`\delta v`$ is present in the perturbed part of the membrane. It is axisymmetrical, and relaxes the concentration difference $`\rho `$ according to the continuity relationseifert  $`_c.\delta 𝐯=d_t\rho `$, or $`\delta v=4\dot{\rho }(1\mathrm{cos}\psi )/(C\mathrm{sin}\psi )`$ (where the dot represents a time derivative, $`_c`$ is the curvilinear gradient along the membrane, and $`\psi `$ is defined Fig.2a. The intermonolayer friction part of energy dissipated per unit time is calculated from Eq.(4):

$$𝒫_{b_m}=\frac{b_m}{4\pi }S^2\dot{\rho }^2\left(\frac{2}{B_d^2}\left(\mathrm{log}\frac{1}{1B_d}B_d\right)\right)$$
(5)
We assume incompressible flows in the membrane and the surrounding fluid. Most of the membrane flow comes from bringing membrane area from the flat membrane into the bud. The flow matches the variation of the area $`\mathrm{\Delta }S=S\pi L^2=SB_d`$, and corresponds to a radial velocity field $`v_{membrane}=d_t(\mathrm{\Delta }S)/(2\pi l)`$ (where $`l`$ is defined Fig.2b). The main source of solvent flow comes from the variation $`\dot{V}`$ of the volume inside the bud, which imposes a flow going through the circular neck of radius $`L`$. In the spherical coordinate system Fig.2c, the velocity field is radial and have the expressionbrenner : $`v_{bulk}=\frac{3\dot{V}}{2\pi r^2}\mathrm{cos}^2\theta `$. The bulk and membrane viscous dissipation are obtained from Eq.(4)

$$𝒫_\eta =\frac{22}{5}\eta \frac{(\dot{V})^2}{\pi L^3};𝒫_{\mu _m}=\mu _m\frac{\left(d_t(\mathrm{\Delta }S)\right)^2}{\pi L^2}$$
(6)
Viscous dissipation in the solvent occurs in both sides of the membrane. $`𝒫_\eta `$ in Eq.(6) is valid for the fluid entering the bud. For the fluid expelled by the bud, the neck size $`L`$ is approximately replaced by the bud radius $`2/C`$ beyond hemispherical bud. Extra sources of dissipation, such as the solvent flow inside the bud, and membrane shear flow in the curving membrane, have been checked not to modify the membrane relaxation qualitatively, and are omitted here for clarity. The evolution of $`S`$ and $`C`$ is entirely determined by Eqs(1, 3, 5, 6). Notwithstanding the simple assumptions for the membrane shape, these equations (Eqs.(10,12)) are fairly complex and have to be dealt with numerically. In the limit of small deformations $`B_d1`$, all equations may be linearized, and membrane viscous dissipation is negligible. The membrane asymmetry relaxes via diffusion along the membrane according to the expression $`S\dot{\rho }=D(\rho dC)`$ with the diffusion coefficient $`D`$ and characteristic relaxation time $`t_0`$ ($`0.1`$ms for $`S_0\mu `$m2):

$$D4\pi \frac{K_s}{b_m}10^8\mathrm{m}^2/\mathrm{s};t_0\frac{S_0}{D}$$
(7)
The influence of the perturbation lengthscale $`S_0`$ is emphasized by using dimensionless variables for area, curvature and time:

$$s\frac{S}{S_0};c\frac{dC}{\rho _0};\tau \frac{t}{t_0}$$
(8)
The new variables are bounded by: $`1<s<\mathrm{}`$ and $`0<c<1`$, and the budding parameter is $`B_d=B_d^{(0)}sc^2`$ (see Eq.(2)). Balancing the curvature forces lead to an equation for $`C`$. The interplay between membrane and solvent dissipation defines a characteristic lengthscale $`\lambda _Dbd^2/\eta `$seifert ; evans ; sens\_electroform , to which the size of the perturbation should be compared.

$$\lambda _D\frac{20\sqrt{\pi }}{11}\frac{bd^2}{\eta };\overline{S_0}\frac{S_0}{\lambda _{D}^{}{}_{}{}^{2}}$$
(9)
This lengthscale $`\lambda _D`$ is of order $`1\mu `$m in water, but is much shorter ($`100`$nm) in biological condition, since the cytosol can be very viscous.

Expressed in the dimensionless variables, the set of equations readsvalidation :

$$\left(\frac{2}{B_d^2}\left(\mathrm{log}\frac{1}{1B_d}B_d\right)\right)\dot{s}=(1sc)$$
(10)
$`\left[\sqrt{\overline{S_0}}{\displaystyle \frac{(12B_d)^2}{(1B_d)^{3/2}}}\left(s^{5/2}\dot{c}+2{\displaystyle \frac{(1B_d)}{(12B_d)}}s^{3/2}c\dot{s}\right)\right]`$ (11)
$`+\left({\displaystyle \frac{\mu _m}{b_md^2}}\right){\displaystyle \frac{B_d}{(1B_d)}}\left(s^2\dot{c}+sc\dot{s}\right)=(1(1+ϵ)sc)`$ (12)
The driving forces for diffusion and membrane deformation (RHS of the above equations) both show the competition between increases of $`s`$ and $`c`$.

At short time ($`s1`$ and $`c1`$), the evolution is given by $`\dot{s}1`$ and $`\dot{c}1/\sqrt{\overline{S_0}}`$. For $`\overline{S_0}<1`$, membrane curvature moves little solvent and occurs faster than diffusion. On the other hand, membrane deformation is slow for $`\overline{S_0}>1`$. For larger deformation however, the membrane viscosity comes into play. It is characterized by a single parameter $`\alpha _m\mu _m/(b_md^2)`$ (typically slightly larger than unitydimova ), and becomes important for small scale perturbations ($`B_d\sqrt{\overline{S_0}}/\alpha _m`$).

Eqs.(10,12) show that membrane deformation will evolve non-monotonously. Indeed, the driving force for diffusion ($`(1sc)`$ \- Eq.(10)) vanishes for complete release of the stretching stress ($`sc=1`$, or $`C=\rho /d`$). On the other hand, the driving force for membrane curvature ($`(1(1+ϵ)sc)`$ \- Eq.(12)) vanishes for smaller deformation because of membrane bending rigidity ($`ϵ\kappa /(2K_sd^2)`$). As a consequence, the budding parameter rises from zero to a maximum value $`B_d^{(max)}`$ over a time $`t_{growth}`$, then it decays slowly to zero over a larger time $`t_{decay}`$. The value of the maximum is a measure of the amount of initial perturbation converted into curvature. It will be discussed extensively in the remaining of this letter, for it determines whether the blister may turn into a well-formed bud before the perturbation diffuses out. For small deformations, the rise occurs over the linear evolution time $`t_{growth}t_0`$, and the decay, mostly driven by bending rigidity, is of order $`t_{decay}t_0/ϵ`$. These times are however much larger in the non-linear regime. To give a feel for the numbers; for $`\overline{S_0}=1`$, the maximum deformation is an hemispherical buds ($`B_d^{(max)}=0.5`$) for an initial perturbation $`B_d^{(0)}=3`$, while nearly completed buds ($`B_d^{(max)}=0.9`$) require $`B_d^{(0)}6`$ (see Fig.3). Fixing $`\lambda _D=1\mu `$m, hemispherical buds have evolution times $`t_{growth}=0.7`$ms and $`t_{decay}=26`$ms, and nearly completed buds $`t_{growth}=7`$ms and $`t_{decay}=300`$ms.

Many results can be extracted from Eqs.(10,12), which determines (within the approximations) the full dynamics of the membrane deformation. Here we concentrate on the following question. How much should we perturb the membrane in order to see buds? Fig.3 shows the value of the initial density of flips, and of the initial perturbation $`B_d^{(0)}`$ needed to obtain a given maximum of the budding parameter $`B_d^{}`$, as a function of $`\overline{S_0}`$. One may practically picture $`B_d^{}`$ as some critical value at which the neck connecting the bud to the mother membrane becomes unstable. More generally, it illustrates the non-trivial competition between membrane and solvent dynamics for large membrane deformation.

Fig.3 shows that membrane viscosity strongly reduces the likeliness of large membrane deformations ($`B_d^{}>0.5`$) for small initial extensions $`\overline{S_0}<1`$. More extended perturbations on the other hand, are dominated by solvent dissipation. Interestingly in this case, the diffusion of the perturbation (increase of $`S`$) promotes bud closure (increase of $`C`$), to minimize the variation of the bud volume ($`\dot{V}=0`$ when $`S\dot{C}(2B_d1)=2C\dot{S}(1B_d)`$). In consequence, a bud is likely to close if it reaches the hemispherical shape, and the results in Fig.3 overlap for $`\overline{S_0}1`$. Furthermore, the density needed to reach a given membrane deformation $`B_d^{}`$ surprisingly tends to a constant value, so the total perturbation mass $`\rho _0S_0`$ linearly increase, as the extension $`S_0`$ increases.

The interplay between membrane and solvent dissipations produces a minimum of $`B_d^{(0)}`$ for a given $`S_0`$ of order $`\lambda _{D}^{}{}_{}{}^{2}`$, purely dictated by dynamics. Mature buds have best chances to be produced at this particular lengthscale, as the maximum membrane deformation $`B_d^{}`$ is closest to the optimal one $`B_d^{(0)}`$. Interestingly, the DNA-induced budding of giant vesiclesagelDNA1  results in endosomes of size close to this optimal dynamical size in water ($`\mu `$m). It is hazardous to make more quantitative comparison with these experiments, since a number of other factors such as the kinetics of DNA adsorption certainly influences the formation of buds, but it is one prediction of the present work that the bud size can be altered by changing the solvent viscosity.

According to Fig.3, well-formed buds with $`B_d=0.9`$ require flipping only $`\rho _03.5\%`$ lipids over an area $`S_01\mu m^2`$ (for $`\lambda _D=1\mu m`$), while it necessitates $`\rho _0=35\%`$ for $`S_0(200nm)^2`$. This amounts to flipping about $`10^5`$ molecules in both cases. The flips need not being perfectly synchronized, as successive events may act cooperatively if they are separated by a time lag shorter than the perturbation decay time $`t_{decay}`$. As already discussed, $`t_{decay}t_0/ϵS_0/(Dϵ)`$ in the limit of small membrane deformation. Note that the evolution becomes much slower in the large deformation regime, where dissipation is very large.

In conclusion, non-linear dynamical equations for the formation of bud-like invaginations in fluid membranes have been derived, and applied to the relaxation of a localized perturbation of the up/down symmetry of lipid bilayers. Non-equilibrium buds may be produced provided that relaxation by membrane curvature occurs faster than the diffusion of the perturbation along the membrane. The membrane response critically depends upon the extension of the initial perturbation, which determines whether the membrane deformation is limited by membrane or solvent dynamics. Bud formation is most likely at the crossover between the two regimes.

###### Acknowledgements.

I thank Albert Johner for many enjoyable discussions.