title: Mechanotransduction pathways linking the extracellular matrix to the nucleus.
abstract: Cells contain several mechanosensing components that transduce mechanical signals into biochemical cascades. During cell-ECM adhesion, a complex network of molecules mechanically couples the extracellular matrix (ECM), cytoskeleton, and nucleoskeleton. The network comprises transmembrane receptor proteins and focal adhesions, which link the ECM and cytoskeleton. Additionally, recently identified protein complexes extend this linkage to the nucleus by linking the cytoskeleton and the nucleoskeleton. Despite numerous studies in this field, due to the complexity of this network, our knowledge of the mechanisms of cell-ECM adhesion at the molecular level remains remarkably incomplete. Herein, we present a review of the structures of key molecules involved in cell-ECM adhesion, along with an evaluation of their predicted roles in mechanical sensing. Additionally, specific binding events prompted by force-induced conformational changes of each molecule are discussed. Finally, we propose a model for the biomechanical events prominent in cell-ECM adhesion.
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California at Berkeley, Berkeley, California, USA.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Jahed
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California at Berkeley, Berkeley, California, USA.
authors.forename: Hengameh
authors.initials: H
authors.lastname: Shams
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California at Berkeley, Berkeley, California, USA.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Mehrbod
authors.affiliation: Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California at Berkeley, Berkeley, California, USA. Electronic address: mofrad@berkeley.edu.
authors.forename: Mohammad R K
authors.initials: MR
authors.lastname: Mofrad
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D064448:Filamins / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016608:Talin / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
chemical_list: C475301:FERMT1 protein, human; D005353:Fibronectins; D064448:Filamins; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016608:Talin; D000185:Actinin; D016596:Vinculin; D005340:Fibrinogen
keywords: Filamin; Focal adhesion; Integrin; Kindlin; LINC complex; Mechanotransduction; Talin; Vinculin