Cells adhere to substrates through mechanosensitive focal adhesion complexes. Measurements that probe how cells detach from substrates when they experience an applied force connect molecular-scale aspects of cell adhesion with the biophysical properties of adherent cells. Such forces can be applied through shear devices that flow fluid in a controlled manner across cells. The signaling pathways associated with focal adhesions, in particular those that involve integrins and receptor tyrosine kinases, are complex, receiving mechano-chemical feedback from the sensing of substrate stiffness as well as of external forces. This article reviews the signaling processes involved in mechanosensing and mechanotransduction during cell-substrate interactions, describing the role such signaling plays in cancer metastasis. We examine some recent progress in quantifying the strength of these interactions, describing a novel fluid shear device that allows for the visualization of the cell and its sub-cellular structures under a shear flow. We also summarize related results from a biophysical model for cellular de-adhesion induced by applied forces. Quantifying cell-substrate adhesions under shear should aid in the development of mechano-diagnostic techniques for diseases in which cell-adhesion is mis-regulated, such as cancers.
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http://dx.doi.org/10.3389/fcell.2019.00251 | DOI Listing |
ACS Nano
January 2025
Biosensor National Special Laboratory, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, PR China.
Single cell adhesion plays a significant role in numerous physiological and pathological processes. Real-time imaging and quantification of single cell adhesion kinetics and corresponding cell-substrate mechanical interaction forces are crucial for elucidating the cellular mechanisms involved in tissue formation, immune responses, and cancer metastasis. Here, we present the development of a plasmonic-based nanomechanical sensing and imaging system (PNMSi) for the real-time measurement of single cell adhesion kinetics and associated nanomechanical forces with plasmonic tracking and monitoring of cell-substrate interactions and the accompanying nanoscale fluctuations.
View Article and Find Full Text PDFMicrosc Res Tech
January 2025
Department of Computer Science, Cihan University, Sulaimaniyah, Kurdistan Region, Iraq.
Waveguide evanescent field fluorescence microscopy (WEFF) is an evanescent-based microscopy that utilizes a confined thin film of light, around 100 nm, to image the plasma membrane of cells attached to a waveguide. Low photobleaching and low background besides its high axial resolution allows time-lapse imaging to investigate changes in cell morphology in the presence or absence of chemical agents. Both large field of view (FOV) and uniform illumination are very important while imaging cell-substrate contacts with an evanescent field.
View Article and Find Full Text PDFComput Biol Med
December 2024
University of Colorado Boulder, Paul M. Rady Department of Mechanical Engineering, Boulder, CO, USA; Biofrontiers Institute, University of Colorado, Boulder, CO, 80309, USA. Electronic address:
Breast cancer cells sense shear stresses in response to interstitial fluid flow in bone and induce specific biological responses. Computational fluid dynamics models have been instrumental in estimating these shear stresses to relate the cell mechanoresponse to exact mechanical signals, better informing experiment design. Most computational models greatly simplify the experimental and cell mechanical environments for ease of computation, but these simplifications may overlook complex cell-substrate mechanical interactions that significantly change shear stresses experienced by cells.
View Article and Find Full Text PDFBMC Genom Data
November 2024
Department Molecular Nephrology, Internal Medicine D (MedD), University Hospital of Münster (UKM), 48149, Münster, Germany.
In epithelia, apicobasal cell polarization is closely linked to cell-cell contact formation, both controlled by the conserved Crumbs (CRB) complex, which includes the transmembrane protein Crumbs (CRB3a) and adapter proteins PALS1, PATJ, and LIN7c. In MDCK II cells, a model for cell polarization, depletion of PALS1 - which binds to all CRB components - leads to defective cell polarization and improper distribution of tight junction proteins, resulting in severe epithelial barrier defects in 3D cyst models. This study investigated whether this phenotype is associated with transcriptional changes by analyzing wildtype (WT) and PALS1 knockout (KO) MDCK II cell lines grown under non-confluent conditions and in 3D cyst cultures.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular Cellular and Developmental Biology, Yale University, 260 Whitney Ave, Yale Science Building 116, New Haven, CT 06511, USA.
Amphipathic helices (AHs) are ubiquitous protein motifs that modulate targeting to organellar membranes by sensing differences in bulk membrane properties. However, the adaptation between membrane-targeting AHs and the nuclear membrane environment that surrounds the genome is poorly understood. Here, we computationally screened for candidate AHs in a curated list of characterized and putative human inner nuclear membrane (INM) proteins.
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