[Paper Review] Actin based propulsion: Intriguing interplay between material properties and growth processes

Karin John, Denis Caillerie+4 more|ArXiv.org|Sep 3, 2009

Cellular Mechanics and Interactions52 references3 citations

TL;DR

This paper presents a theoretical framework linking actin polymerization dynamics and mechanical properties in actin-based propulsion, showing that asymmetric force generation arises from the interplay between gel elasticity, polymerization kinetics at the brush interface, and viscous dissipation. The key result is that object motion emerges not from active forces alone but from frictional asymmetry and treadmilling, with object velocity determined by the ratio of friction coefficients, explaining observed speeds close to treadmilling rates in low-Reynolds-number environments.

ABSTRACT

Eukaryotic cells and intracellular pathogens such as bacteria or viruses utilize the actin polymerization machinery to propel themselves forward. Thereby, the onset of motion and choice of direction may be the result of a spontaneous symmetry-breaking or might be triggered by external signals and preexisting asymmetries, e.g. through a previous septation in bacteria. Although very complex, a key feature of cellular motility is the ability of actin to form dense polymeric networks, whose microstructure is tightly regulated by the cell. These polar actin networks produce the forces necessary for propulsion but may also be at the origin of a spontaneous symmetry-breaking. Understanding the exact role of actin dynamics in cell motility requires multiscale approaches which capture at the same time the polymer network structure and dynamics on the scale of a few nanometers and the macroscopic distribution of elastic stresses on the scale of the whole cell. In this chapter we review a selection of theories on how mechanical material properties and growth processes interact to induce the onset of actin based motion.

Motivation & Objective

• To understand the mechanical origin of directed motion in actin-based propulsion systems, particularly in eukaryotic cells and intracellular pathogens.
• To resolve the paradox of how motion initiates spontaneously in the absence of external forces, despite negligible inertial effects (Re ≪ 1).
• To bridge the gap between microscopic polymerization dynamics at the actin brush and macroscopic stress distributions in the actin gel.
• To integrate elastic instabilities and reaction-diffusion signaling into a unified model of cellular motility.

Proposed method

• Develops a homogenization model to describe the complex microstructure of actin gels while retaining a continuous mechanical framework for stress distribution.
• Analyzes the stability of actin gels growing from curved surfaces, identifying undulating and peristaltic instabilities based on mode number (m ≤ 4 vs. m > 4).
• Uses a force balance model in the viscous regime, assuming linear drag with friction coefficients ξₒ and ξc for the object and actin comet, respectively.
• Derives the object velocity as vₒ = vₜ ξc / (ξₒ + ξc), where vₜ is the treadmilling speed, showing motion arises from friction asymmetry.
• Proposes coupling between homogenized gel mechanics and dynamic polymerization at the brush, as in EGF08 and GFF08, to model complex geometries like the leading edge.
• Considers the role of signaling cascades modeled as reaction-diffusion systems that induce cell polarization and regulate actin activity.

Experimental results

Research questions

• RQ1 How can directed motion emerge from actin polymerization in the absence of external forces in a viscous, low-Reynolds-number environment?
• RQ2 What is the role of friction asymmetry between the propelled object and the actin comet in determining the object's velocity?
• RQ3 How do elastic instabilities in the actin gel couple to polymerization dynamics at the brush interface to drive symmetry breaking?
• RQ4 In what way do reaction-diffusion signaling systems and mechanical instabilities co-evolve to establish and maintain cell polarity?
• RQ5 How can a unified model bridge the gap between nanoscale polymerization kinetics and macroscale stress fields in actin-based motility?

Key findings

• Motion in actin-based propulsion is driven not by active force generation alone, but by viscous dissipation and frictional asymmetry between the object and the actin comet.
• The object velocity is given by vₒ = vₜ ξc / (ξₒ + ξc), showing that motion is determined by the ratio of friction coefficients, not by absolute force magnitudes.
• In the limit where the actin comet has much higher friction (ξc ≫ ξo), the object velocity approaches the treadmilling speed vₜ, consistent with experimental observations.
• For small mode numbers (m ≤ 4), the system exhibits an undulating instability with in-phase perturbations at internal and external interfaces; for higher modes, a peristaltic instability with out-of-phase modes emerges.
• Theoretical models must couple homogenized gel mechanics with dynamic brush kinetics to capture the full complexity of actin gel growth and deformation in realistic geometries.
• The integration of reaction-diffusion signaling and mechanical instabilities remains an open challenge, though both are essential for robust cell polarization and motility.