Many of the cell membrane's vital functions are achieved by the selforganization of the proteins and biopolymers embedded in it. The protein dynamics is in part determined by its drag. A large number of these proteins can polymerize to form filaments.
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In vitro studies of protein–membrane interactions often involve using rigid beads coated with lipid bilayers, as a model for the cell membrane. Motivated by this, we use slenderbody theory to compute the translational and rotational resistance of a single filamentous protein embedded in the outer layer of a supported bilayer membrane and surrounded on the exterior by a Newtonian fluid. We first consider the regime where the two layers are strongly coupled through their interleaflet friction. We find that the drag along the parallel direction grows linearly with the filament's length and quadratically with the length for the perpendicular and rotational drag coefficients. These findings are explained using scaling arguments and by analysing the velocity fields around the moving filament. We then present and discuss the qualitative differences between the drag of a filament moving in a freely suspended bilayer and a supported membrane as a function of the membrane's interleaflet friction. Finally, we briefly discuss how these findings can be used in experiments to determine membrane rheology. In summary, we present a formulation that allows computation of the effects of membrane properties (its curvature, viscosity and interleaflet friction), and the exterior and interior threedimensional fluids’ depth and viscosity on the drag of a rodlike/filamentous protein, all in a unified theoretical framework.Free, publiclyaccessible full text available January 25, 2025 
Few techniques are available for studying the nature of forces that drive subcellular dynamics. Here we develop two complementary ones. The first is femtosecond stereotactic laser ablation, which rapidly creates complex cuts of subcellular structures and enables precise dissection of when, where and in what direction forces are generated. The second is an assessment of subcellular fluid flows by comparison of direct flow measurements using microinjected fluorescent nanodiamonds with largescale fluidstructure simulations of different force transduction models. We apply these techniques to study spindle and centrosome positioning in early Caenorhabditis elegans embryos and to probe the contributions of microtubule pushing, cytoplasmic pulling and cortical pulling upon centrosomal microtubules. Based on our results, we construct a biophysical model to explain the dynamics of centrosomes. We demonstrate that cortical pulling forces provide a general explanation for many behaviours mediated by centrosomes, including pronuclear migration and centration, rotation, metaphase spindle positioning, asymmetric spindle elongation and spindle oscillations. This work establishes methodologies for disentangling the forces responsible for cell biological phenomena.more » « lessFree, publiclyaccessible full text available January 25, 2025

The cell cytoskeleton is a dynamic assembly of semiflexible filaments and motor proteins. The cytoskeleton mechanics is a determining factor in many cellular processes, including cell division, cell motility and migration, mechanotransduction and intracellular transport. Mechanical properties of the cell, which are determined partly by its cytoskeleton, are also used as biomarkers for disease diagnosis and cell sorting. Experimental studies suggest that in whole cell scale, the cell cytoskeleton and its permeating cytosol may be modelled as a twophase poroviscoelastic (PVE) material composed of a viscoelastic (VE) network permeated by a viscous cytosol. We present the first general solution to this twophase system in spherical coordinates, where we assume that both the fluid and network phases are in their linear response regime. Specifically, we use generalized linear incompressible and compressible VE constitutive equations to describe the stress in the fluid and network phases, respectively. We assume a constant permeability that couples the fluid and network displacements. We use these general solutions to study the motion of a rigid sphere moving under a constant force inside a twophase system, composed of a linear elastic network and a Newtonian fluid. It is shown that the network compressibility introduces a slow relaxation of the sphere and nonmonotonic network displacements with time along the direction of the applied force. Our results can be applied to particletracking microrheology to differentiate between PVE and VE materials, and to measure the fluid permeability as well as VE properties of the fluid and the network phases.more » « less

Dynamic organization of the cytoskeletal filaments and rodlike proteins in the cell membrane and other biological interfaces occurs in many cellular processes. Previous modeling studies have considered the dynamics of a single rod on fluid planar membranes. We extend these studies to the more physiologically relevant case of a single filament moving in a spherical membrane. Specifically, we use a slenderbody formulation to compute the translational and rotational resistance of a single filament of length L moving in a membrane of radius R and 2D viscosity ηm, and surrounded on its interior and exterior with Newtonian fluids of viscosities η− and η+. We first discuss the case where the filament's curvature is at its minimum κ=1/R. We show that the boundedness of spherical geometry gives rise to flow confinement effects that increase in strength with increasing the ratio of filament's length to membrane radius L/R. These confinement flows only result in a mild increase in filament's resistance along its axis, ξ∥, and its rotational resistance, ξΩ. As a result, our predictions of ξ∥ and ξΩ can be quantitatively mapped to the results on a planar membrane. In contrast, we find that the drag in perpendicular direction, ξ⊥, increases superlinearly with the filament's length, when L/R>1 and ultimately ξ⊥→∞ as L/R→π. Next, we consider the effect of the filament's curvature, κ, on its parallel motion, while fixing the membrane's radius. We show that the flow around the filament becomes increasingly more asymmetric with increasing its curvature. These flow asymmetries induce a net torque on the filament, coupling its parallel and rotational dynamics. This coupling becomes stronger with increasing L/R and κ.more » « less