Hindrances to precise recovery of cellular forces in fibrous biopolymer networks

TL;DR

This paper investigates the challenges in accurately recovering cell-generated forces in fibrous biopolymer networks, highlighting key issues like irregular traction patterns and network uncertainties that hinder precise force measurement.

Contribution

It identifies specific factors that impede force recovery in fibrous ECMs and discusses potential strategies to overcome these limitations.

Findings

Irregular traction patterns cause large errors in force estimation.

Uncertainty in fiber stiffness affects force recovery accuracy.

Non-affine deformations and unknown network topology hinder precise force determination.

Abstract

How cells move through the three-dimensional extracellular matrix (ECM) is of increasing interest in attempts to understand important biological processes such as cancer metastasis. Just as in motion on flat surfaces, it is expected that experimental measurements of cell-generated forces will provide valuable information for uncovering the mechanisms of cell migration. However, the recovery of forces in fibrous biopolymer networks may suffer from large errors. Here, within the framework of lattice-based models, we explore possible issues in force recovery by solving the inverse problem: how can one determine the forces cells exert to their surroundings from the deformation of the ECM? Our results indicate that irregular cell traction patterns, the uncertainty of local fiber stiffness, the non-affine nature of ECM deformations and inadequate knowledge of network topology will all prevent the precise force determination. At the end, we discuss possible ways of overcoming these difficulties.