Differential regulation of GUV mechanics via actin network architectures.

Actin networks polymerize and depolymerize to construct highly organized structures, thereby endowing the mechanical phenotypes found in a cell. It is generally believed that the amount of filamentous actin and actin network architecture determine cytoplasmic viscoelasticity of the whole cell. However, the intrinsic complexity of a cell and the presence of endogenous cellular components make it difficult to study the differential roles of distinct actin networks in regulating cell mechanics. Here, we model a cell by using giant unilamellar vesicles (GUVs) encapsulating actin filaments and networks assembled by various actin cross-linker proteins. Perturbation of these cytoskeletal vesicles using alternating current electric fields revealed that deformability depends on actin network architecture. While actin-free vesicles exhibited large electromechanical deformations, deformations of GUVs encapsulating actin filaments were significantly dampened. The suppression of electrodeformation of actin-GUVs can be similarly recapitulated by using aqueous poly(ethylene glycol) 8000 solutions at different concentrations to modulate solution viscoelasticity. Furthermore, networks cross-linked by alpha actinin resulted in decreased GUV deformability compared with actin-filament-encapsulating GUVs, and membrane-associated actin networks, through the formation of the dendritic actin cortex, greatly dampened electrodeformation of GUVs. These results highlight that the organization of actin networks regulates the mechanics of GUVs and shed insights into the origin of differential deformability of cells.

Gating of a mechanosensitive channel due to cellular flows.

A multiscale continuum model is constructed for a mechanosensitive (MS) channel gated by tension in a lipid bilayer membrane under stresses due to fluid flows. We illustrate that for typical physiological conditions vesicle hydrodynamics driven by a fluid flow may render the membrane tension sufficiently large to gate a MS channel open. In particular, we focus on the dynamic opening/closing of a MS channel in a vesicle membrane under a planar shear flow and a pressure-driven flow across a constriction channel. Our modeling and numerical simulation results quantify the critical flow strength or flow channel geometry for intracellular transport through a MS channel. In particular, we determine the percentage of MS channels that are open or closed as a function of the relevant measure of flow strength. The modeling and simulation results imply that for fluid flows that are physiologically relevant and realizable in microfluidic configurations stress-induced intracellular transport across the lipid membrane can be achieved by the gating of reconstituted MS channels, which can be useful for designing drug delivery in medical therapy and understanding complicated mechanotransduction.

Dynamics of a multicomponent vesicle in shear flow.

We study the fully nonlinear, nonlocal dynamics of two-dimensional multicomponent vesicles in a shear flow with matched viscosity of the inner and outer fluids. Using a nonstiff, pseudo-spectral boundary integral method, we investigate dynamical patterns induced by inhomogeneous bending for a two phase system. Numerical results reveal that there exist novel phase-treading and tumbling mechanisms that cannot be observed for a homogeneous vesicle. In particular, unlike the well-known steady tank-treading dynamics characterized by a fixed inclination angle, here the phase-treading mechanism leads to unsteady periodic dynamics with an oscillatory inclination angle. When the average phase concentration is around 1/2, we observe tumbling dynamics even for very low shear rate, and the excess length required for tumbling is significantly smaller than the value for the single phase case. We summarize our results in phase diagrams in terms of the excess length, shear rate, and concentration of the soft phase. These findings go beyond the well known dynamical regimes of a homogeneous vesicle and highlight the level of complexity of vesicle dynamics in a fluid due to heterogeneous material properties.

Dynamics of a compound vesicle in shear flow.

The dynamics of a compound vesicle (a lipid bilayer membrane enclosing a fluid with a suspended particle) in shear flow is investigated by using both numerical simulations and theoretical analysis. We find that the nonlinear hydrodynamic interaction between the inclusion and the confining membrane gives rise to new features of the vesicle dynamics: The transition from tank treading to tumbling can occur in the absence of any viscosity mismatch, and a vesicle can swing if the enclosed particle is nonspherical. Our results highlight the complex effects of internal cellular structures have on cell dynamics in microcirculatory flows. For example, parasites in malaria-infected erythrocytes increase cytoplasmic viscosity, which leads to increase in blood viscosity.

Equilibrium shapes of planar elastic membranes.

Using a rod theory formulation, we derive equations of state for a thin elastic membrane subjected to several different boundary conditions-clamped, simply supported, and periodic. The former is applicable to membranes supported on a softer substrate and subjected to uniaxial compression. We show that a wider family of quasistatic equilibrium shapes exist beyond the previously obtained analytical solutions. In the latter case of periodic membranes, we were able to derive exact solutions in terms of elliptic functions. These equilibria are verified by considering a fluid-structure interaction problem of a periodic, length-preserving bilipid membrane modeled by the Helfrich energy immersed in a viscous fluid. Starting from an arbitrary shape, the membrane dynamics to equilibrium are simulated using a boundary integral method.