In silico CDM model sheds light on force transmission in cell from focal adhesions to nucleus.
Cell adhesion is crucial for many types of cell, conditioning differentiation, proliferation, and protein synthesis. As a mechanical process, cell adhesion involves forces exerted by the cytoskeleton and transmitted by focal adhesions to extracellular matrix. These forces constitute signals that infer specific biological responses. Therefore, analyzing mechanotransduction during cell adhesion could lead to a better understanding of the mechanobiology of adherent cells. For instance this may explain how, the shape of adherent stem cells influences their differentiation or how the stiffness of the extracellular matrix affects adhesion strength. To assess the mechanical signals involved in cell adhesion, we computed intracellular forces using the Cytoskeleton Divided Medium model in endothelial cells adherent on micropost arrays of different stiffnesses. For each cell, focal adhesion location and forces measured by micropost deflection were used as an input for the model. The cytoskeleton and the nucleoskeleton were computed as systems of multiple tensile and compressive interactions. At the end of computation, the systems respected mechanical equilibrium while exerting the exact same traction force intensities on focal adhesions as the observed cell. The results indicate that not only the level of adhesion forces, but also the shape of the cell has an influence on intracellular tension and on nucleus strain. The combination of experimental micropost technology with the present CDM model constitutes a tool able to estimate the intracellular forces.
Aix Marseille Univ, CNRS, ISM, Inst Movement Sci, Marseille, France; APHM, Sainte-Marguerite Hospital, Institute for Locomotion, Department of Orthopaedics and Traumatology, Marseille, France. Electronic address: jean-louis.milan@univ-amu.fr.
Jean-Louis
JL
Milan
Aix Marseille Univ, CNRS, ISM, Inst Movement Sci, Marseille, France; APHM, Sainte-Marguerite Hospital, Institute for Locomotion, Department of Orthopaedics and Traumatology, Marseille, France.
Ian
I
Manifacier
University of Washington, Seattle, WA, USA.
Kevin M
KM
Beussman
University of Washington, Seattle, WA, USA.
Sangyoon J
SJ
Han
University of Washington, Seattle, WA, USA.
Nathan J
NJ
Sniadecki
Aix Marseille Univ, CNRS, ISM, Inst Movement Sci, Marseille, France; APHM, Sainte-Marguerite Hospital, Institute for Locomotion, Department of Orthopaedics and Traumatology, Marseille, France.
Imad
I
About
Aix Marseille Univ, CNRS, ISM, Inst Movement Sci, Marseille, France; APHM, Sainte-Marguerite Hospital, Institute for Locomotion, Department of Orthopaedics and Traumatology, Marseille, France.
Patrick
P
Chabrand
D002448:Cell Adhesion; D002467:Cell Nucleus / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D003599:Cytoskeleton / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological
Computational modeling; Cytoskeleton; Divided medium mechanics; Mechanobiology; Mechanotransduction; Microposts; Nucleus deformation; Substrate stiffness