Thermal fluctuations of vesicles and nonlinear curvature elasticity—implications for size-dependent renormalized bending rigidity and vesicle size distribution

Abstract

Both closed and open biological membranes noticeably undulate at physiological temperatures. These thermal fluctuations influence a broad range of biophysical phenomena, ranging from self-assembly to adhesion. In particular, the experimentally measured thermal fluctuation spectra also provide a facile route to the assessment of mechanical and certain other physical properties of biological membranes. The theoretical assessment of thermal fluctuations, be it for closed vesicles or the simpler case of flat open lipid bilayers, is predicated upon assuming that the elastic curvature energy is a quadratic functional of the curvature tensor. However, a qualitatively correct description of several phenomena such as binding–unbinding transition, vesicle-to-bicelle transition, appearance of hats and saddles among others, appears to require consideration of constitutively nonlinear elasticity that includes fourth order curvature contributions rather than just quadratic. In particular, such nonlinear considerations are relevant in the context of large-curvature or small-sized vesicles. In this work we discuss the statistical mechanics of closed membranes (vesicles) incorporating both constitutive and geometrical nonlinearities. We derive results for the renormalized bending rigidity of small vesicles and show that significant stiffening may occur for sub-20 nm vesicle sizes. Our closed-form results may also be used to determine nonlinear curvature elasticity properties from either experimentally measured fluctuation spectra or microscopic calculations such as molecular dynamics. Finally, in the context of our results on thermal fluctuations of vesicles and nonlinear curvature elasticity, we reexamine the problem of determining the size distribution of vesicles and obtain results that reconcile well with experimental observations. However, our results are somewhat paradoxical. Specifically, the molecular dynamics predictions for the thermo-mechanical behavior of small vesicles of prior studies appear to be inconsistent with the nonlinear elastic properties that we estimate by fitting to the experimentally determined vesicle size-distribution trends and data.