Statistical mechanics of active vesicles and the size distribution paradox

Abstract

Vesicles are the primary modes of communication and transport in cell biology. Conventional wisdom based on thermodynamic equilibrium says that vesicles should have a certain minimum size and size distribution dictated by their thermal fluctuations. However, there is compelling experimental evidence that vesicles exhibit a vast variety of size distributions depending on their formation process and function which cannot be explained by equilibrium statistical mechanics alone. We investigate a non-equilibrium statistical mechanics-based model to understand the role of active membranes on the size distribution of vesicles. Active membranes contain proteins that use external energy sources, such as adenosine triphosphate hydrolysis, and are known to exert forces on the membrane during their activity to carry out different biological functions. The central idea behind our model is that activity, attributed to different sources, impacts vesicle fluctuations in two opposing ways — by active noise which enhances fluctuations, and membrane tension which decreases fluctuations. The interplay of active fluctuations and active tension endows the vesicles with the ability to achieve size distributions that are deemed improbable by equilibrium statistical mechanics. We show that our model for active vesicles, based on linearized curvature elasticity, can reproduce different experimental data for vesicle size distributions available in the literature by varying the activity. Elucidating how these vesicles achieve such diverse size distributions can open avenues for a deeper understanding of physiological and pathological processes and help design vesicles for diagnostics and drug delivery applications.