A computational framework for modeling cell–matrix interactions in soft biological tissues

• Main Authors: Aydin, R.C (Author), Cyron, C.J (Author), Eichinger, J.F (Author), Grill, M.J (Author), Humphrey, J.D (Author), Kermani, I.D (Author), Wall, W.A (Author)
• Format: Article
• Language: English
• Published: Springer Science and Business Media Deutschland GmbH 2021
• Subjects: Actin Cytoskeleton; actin filament; Article; biological model; Biomechanical Phenomena; biomechanics; cell communication; Cell Communication; cell density; cell matrix interaction; cell–extracellular matrix interaction; chemistry; collagen; Collagen; Computational framework; computer language; computer simulation; Computer Simulation; conceptual framework; controlled study; cross linking; cytoskeleton; Cytoskeleton; degradation; discrete fiber model; elastin; Elastin; Extracellular fibers; Extracellular matrices; extracellular matrix; Extracellular Matrix; finite element analysis; Finite Element Analysis; finite element method; growth and remodeling; Histology; homeostasis; Homeostasis; human; Humans; integrin; Integrins; Markov chain; mathematical computing; mechanical homeostasis; Mechanical homeostasis; mechanical stress; Mechanisms; metabolism; Micromechanical mechanisms; Models, Biological; Molecular clutches; Physiological process; physiology; Programming Languages; Proteins; rigidity; Soft biological tissue; soft tissue; Stochastic Processes; Stress, Mechanical; tension; Three dimensional computer graphics; Tissue
• Online Access: View Fulltext in Publisher

 Living soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis. © 2021, The Author(s).