Durotaxis: the mechanical control of directed cell migration

Abstract

Directed cell migration is essential for cells to efficiently migrate in physiological and pathological processes. While migrating in their native environment, cells interact with multiple types of cues, such as mechanical and chemical signals. The role of chemical guidance via chemotaxis has been studied in the past, the understanding of mechanical guidance of cell migration via durotaxis remained unclear until very recently. Nonetheless, durotaxis has become a topic of intensive research and several advances have been made in the study of mechanically guided cell migration across multiple fields. Thus, in this article we provide a state of the art about durotaxis by discussing in silico, in vitro and in vivo data. We also present insights on the general mechanisms by which cells sense, transduce and respond to environmental mechanics, to then contextualize these mechanisms in the process of durotaxis and explain how cells bias their migration in anisotropic substrates. Furthermore, we discuss what is known about durotaxis in vivo and we comment on how haptotaxis could arise from integrating durotaxis and chemotaxis in native environments.

Mathematical models of neuronal growth

“…This early phase, known as axon guidance (or pathfinding), crucially relies on cues from the environment which are processed to instruct growth cone trajectory. This includes chemotaxis primarily, i.e., guidance of axons by gradients of diffusing chemicals like Slits or Netrins (Mortimer et al 2008;Plachez and Richards 2005;Chilton 2006); but also haptotaxis, i.e., guidance by gradients in adhesion or substrate-bound chemicals (Sundararaghavan et al 2011); durotaxis (or mechanotaxis), i.e., guidance by gradients in substrate stiffness (Abuwarda and Pathak 2020;Koser et al 2016;Espina et al 2021); electrotaxis (or galvanotaxis), i.e., guidance by electric field (Yao and Li 2016;Hamid and Hayek 2008;Gokoffski et al 2019;Shapiro et al 2005); curvotaxis, i.e., guidance by substrate curvature (Smeal et al 2005); or guidance assisted by guidepost cells such as radial glial cells (Franze et al 2009b;Rakic 1972) or Schwann cells (Thompson and Buettner 2006). The growth cone is the main sensory structure at play in all these guidance modalities.…”

Cancer Cell Motility Through Unjamming Impacts Metastatic Risk

“…It is only possible for cancer cells to escape from the depth of a cluster if unjamming occurs. The outer cells of our clusters are in contact with the fibrotic ECM, which is highly attractive to cancer cells through mechanotransduction and durotaxis as tumour promoters [39,40].…”

Unravelling cell migration: defining movement from the cell surface

“…Nevertheless, it is imperative to analyze them at different scales as well as their interactions with each other [ 176 , 229 , 367 , 370 ]. For instance, mechanosensing must happen in milliseconds, while protein modifications mediating mechanotransduction occur in seconds to minutes, and the associated transcriptional responses require minutes to hours to happen [ 23 ]. Accordingly, novel protocols, methodologies, and techniques for quantitative analysis of these components and events are still required.…”

“…Another source of complexity in the study of cell migration is that its regulation depends on the biochemical and biophysical features of the pericellular space [ 22 ]. Therefore, cells must integrate concurrent, potentially cooperative, or opposing inputs in their decision-making process [ 23–26 ]. These external cues can modulate cellular properties and events, from cell shape and polarity to cell–cell and cell–matrix interactions.…”