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How active are red blood cells?

RBC active

One of the first observations of red blood cells (RBC) by optical microscopy during the 19th century was the "vibrating" fluctuation of its plasma membrane .
This phenomenon of flickering was first consider to be a signal of living matter, but later explained as thermal (passive) fluctuations of the cell membrane.
Recent studies have indicated the involvement of non-equilibrium processes. However, the fundamental
question whether membrane fluctuations are driven by an active process or simply by thermal agitation remains controversial.

Using active and passive microrheology to directly compare the membrane response and fluctuations on single erythrocytes, we have studied the
violation of the fluctuation–dissipation relation, which is a direct demonstration of the non-equilibrium nature of flickering. Simulations show that several
molecular mechanisms may explain the active fluctuations, and we predict their kinetics. Candidates are metabolic activity in the cytoskeletal spectrin network,
and active force dipoles induced by ion pumps in the plasma membrane.

(D.A. Fedosov, T. Auth & G. Gompper)




Minimal Model of Cell Motility

Actin polymerization is the mechanism that dominates cell motility in mesenchymal migration. Actin filaments attach via receptors to the substrate over which the cell is crawling, and polymerize/depolymerize at their plus/minus ends, which makes the filaments grow or shrink, and exert forces on the cell membrane. Due to the forces at the edge of a motile cell, the cell can move and change shape. For example, the aspect ratio of keratocytes increases with the ordering of the actin network and the actin density along the leading edge.

cell motility


We propose a composite active particle -- consisting of quasi-two-dimensional self-propelled rods confined inside a rigid motile ring -- to study cell migration. Here, the basic idea is to mimic the dynamics and forces of cytoskeletal filaments by rod-like self-propelled particles: actin and microtubule treadmilling and polymerization forces are modeled by the self-propulsion of rigid rods with constant length.
This system is studied by Brownian Dynamics simulations to elucidate the different kinds of motion that the complex self-propelled rings displays, which are persistent motion, random motion, circling, and run-and-circle motion -- depending on the rod-alignment interaction and the number of rods. Indeed, these motion patterns are also observed for motility of cells on a substrate.

(C.A. Velasco, T. Auth & G. Gompper)



For Microtubule Sliding, One Arm Is Better Than Two

The versatile cytoskeletal network in eukaryotic cells would be lifeless if not for kinesin motor proteins, which attach to and walk on microtubules. These motor proteins have arms that can crosslink adjacent polar filaments, and move along them. This causes the motors to stretch, and when multiple motors crosslink two microtubules, the cooperative effect of these motors results in a sliding stress that transports these microtubule relative to each other. In cells, this mechanism is important for cell-scale cytoplasmic flows, faster distribution of molecules and organelles, and the determination of cell shape.

motor filament

Using two-dimensional Brownian dynamics simulations, we study a dense, confined mixture of rigid microtubules (MTs) and motors that move unidirectionally on them. We show that one-arm motors, with a motile arm on only one of the two MTs, produce large polarity-sorted MT clusters, while two-arm motors, with motile arms on both microtubules, produce bundles. One-armed motors also induce, on average, higher velocities between anti-aligned MTs than two-armed motors. Our results, where MTs move faster near the confining wall, are consistent with experimental observations in Drosophila oocytes, where enhanced microtubule activity is found close to the confining plasma membrane.

(A. Ravichandran, G. A. Vliegenthart, G. Saggiorato, T. Auth & G. Gompper)



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