title: Primary cilia mechanics affects cell mechanosensation: A computational study.
abstract: Primary cilia (PC) are mechanical cell structures linked to the cytoskeleton and are central to how cells sense biomechanical signals from their environment. However, it is unclear exactly how PC mechanics influences cell mechanosensation. In this study we investigate how the PC mechanical characteristics are involved in the mechanotransduction process whereby cilium deflection under fluid flow induces strains on the internal cell components that regulate the cell׳s mechanosensitive response. Our investigation employs a computational approach in which a finite element model of a cell consisting of a nucleus, cytoplasm, cortex, microtubules, actin bundles and a primary cilium was used together with a finite element representation of a flow chamber. Fluid-structure interaction analysis was performed by simulating perfusion flow of 1mm/s on the cell model. Simulations of cells with different PC mechanical characteristics, showed that the length and the stiffness of PC are responsible for the transmission of mechanical stimuli to the cytoskeleton. Fluid flow deflects the cilium, with the highest strains found at the base of the PC and in the cytoplasm. The PC deflection created further strains on the cell nucleus but did not influence microtubules and actin bundles significantly. Our results indicate that PC deflection under fluid flow stimulation transmits mechanical strain primarily to other essential organelles in the cytoplasm, such as the Golgi complex, that regulate cells' mechanoresponse. The simulations further suggest that cell mechanosensitivity can be altered by targeting PC length and rigidity.
authors.affiliation: INSIGNEO - Institute for in silico medicine, Department of Mechanical Engineering, The University of Sheffield, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, United Kingdom; Department of Biomedical Engineering, Lund University, Lund, Sweden.
authors.forename: Hanifeh
authors.initials: H
authors.lastname: Khayyeri
authors.affiliation: INSIGNEO - Institute for in silico medicine, Department of Mechanical Engineering, The University of Sheffield, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Barreto
authors.affiliation: INSIGNEO - Institute for in silico medicine, Department of Mechanical Engineering, The University of Sheffield, Sir Frederick Mappin Building, Mappin Street, Sheffield S1 3JD, United Kingdom. Electronic address: d.lacroix@sheffield.ac.uk.
authors.forename: Damien
authors.initials: D
authors.lastname: Lacroix
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological
keywords: Biophysics; Cell mechanics; Finite element model; Mechanobiology; Mechanosensation