A multi-scale clutch model for adhesion complex mechanics

Chiara Venturini and Pablo Sáez

PLOS Computational Biology, 2023, vol. 19, issue 7, 1-26

Abstract: Cell-matrix adhesion is a central mechanical function to a large number of phenomena in physiology and disease, including morphogenesis, wound healing, and tumor cell invasion. Today, how single cells respond to different extracellular cues has been comprehensively studied. However, how the mechanical behavior of the main individual molecules that form an adhesion complex cooperatively responds to force within the adhesion complex is still poorly understood. This is a key aspect of cell adhesion because how these cell adhesion molecules respond to force determines not only cell adhesion behavior but, ultimately, cell function. To answer this question, we develop a multi-scale computational model for adhesion complexes mechanics. We extend the classical clutch hypothesis to model individual adhesion chains made of a contractile actin network, a talin rod, and an integrin molecule that binds at individual adhesion sites on the extracellular matrix. We explore several scenarios of integrins dynamics and analyze the effects of diverse extracellular matrices on the behavior of the adhesion molecules and on the whole adhesion complex. Our results describe how every single component of the adhesion chain mechanically responds to the contractile actomyosin force and show how they control the traction forces exerted by the cell on the extracellular space. Importantly, our computational results agree with previous experimental data at the molecular and cellular levels. Our multi-scale clutch model presents a step forward not only to further understand adhesion complexes mechanics but also to impact, e.g., the engineering of biomimetic materials, tissue repairment, or strategies to arrest tumor progression.Author summary: Cell-matrix adhesions are directly implicated in key biological processes such as tissue development, regeneration, and tumor cell invasion. This cell function is determined by how adhesion complexes feel and respond to mechanical forces. Still, how forces are transmitted through the individual cell adhesion molecules that integrate the adhesion complex is poorly understood. To address this issue, we develop a multi-scale clutch model for adhesion complexes where individual adhesion chains, made of integrin and talin molecules, are considered within classical clutch models. This approach provides a rich mechanosensing insight into how the mechanics of cell adhesion works. It allows the integration of accurate biophysical models of individual adhesion molecules into whole adhesion complex models. Our multi-scale clutch approach extends the current knowledge of adhesion complexes and also impacts current strategies for tissue regeneration, control of tumor progression, and engineering biomimetic materials.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011250 (text/html)
https://journals.plos.org/ploscompbiol/article/fil ... 11250&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1011250

DOI: 10.1371/journal.pcbi.1011250

Access Statistics for this article

More articles in PLOS Computational Biology from Public Library of Science
Bibliographic data for series maintained by ploscompbiol ().