title: Cellular adaptation to biomechanical stress across length scales in tissue homeostasis and disease.
abstract: Human tissues are remarkably adaptable and robust, harboring the collective ability to detect and respond to external stresses while maintaining tissue integrity. Following injury, many tissues have the capacity to repair the damage - and restore form and function - by deploying cellular and molecular mechanisms reminiscent of developmental programs. Indeed, it is increasingly clear that cancer and chronic conditions that develop with age arise as a result of cells and tissues re-implementing and deregulating a selection of developmental programs. Therefore, understanding the fundamental molecular mechanisms that drive cell and tissue responses is a necessity when designing therapies to treat human conditions. Extracellular matrix stiffness synergizes with chemical cues to drive single cell and collective cell behavior in culture and acts to establish and maintain tissue homeostasis in the body. This review will highlight recent advances that elucidate the impact of matrix mechanics on cell behavior and fate across these length scales during times of homeostasis and in disease states.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Electronic address: penney.gilbert@utoronto.ca.
authors.forename: Penney M
authors.initials: PM
authors.lastname: Gilbert
authors.affiliation: Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco (UCSF), San Francisco, CA, USA; Department of Anatomy and Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, CA, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCSF, San Francisco, CA, USA; UCSF Helen Diller Comprehensive Cancer Center, UCSF, San Francisco, CA, USA.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Weaver
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001696:Biomechanical Phenomena; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D003285:Contractile Proteins / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D013314:Stress, Mechanical
chemical_list: D015820:Cadherins; D003285:Contractile Proteins
keywords: Actin-myosin contractility; Biomechanics; Cancer; Cell contractility; Development; EMT; Intracellular tension; Matrix stiffness; Mechanical force; Mechanical memory; Mechanosensing; Mechanotransduction; Tissue homeostasis; Tissue tension