Cell adhesion strength and tractions are mechano-diagnostic features of cellular invasiveness. Issue 23 (25th May 2022)

• Record Type: Journal Article
• Authors: Paddillaya, Neha; Ingale, Kalyani; Gaikwad, Chaitanya; Saini, Deepak Kumar; Pullarkat, Pramod; Kondaiah, Paturu; Menon, Gautam I.; Gundiah, Namrata
• Is Part Of: Soft matter. Volume 18:Issue 23(2022)
• Page Start: 4378
• Page End: 4388
• Publication Date: 2022-05-25
• Subjects: Soft condensed matter -- Periodicals; 530.413
• DOI: 10.1039/d2sm00015f
• Languages: English
• ISSNs: 1744-683X

Abstract

Abstract : Invasive cells show significantly lower critical de-adhesion strength, and high cell spread areas when adhered to substrates, as compared to non-invasive cells which are characterized by low tractions and high de-adhesion strengths. Abstract : The adhesion of cells to substrates occurs via integrin clustering and binding to the actin cytoskeleton. Oncogenes modify anchorage-dependent mechanisms in cells during cancer progression. Fluid shear devices provide a label-free way to characterize cell–substrate interactions and heterogeneities in cell populations. We quantified the critical adhesion strengths of MCF-7, MDAMB-231, A549, HPL1D, HeLa, and NIH3T3 cells using a custom fluid shear device. The detachment response was sigmoidal for each cell type. A549 and MDAMB-231 cells had significantly lower critical adhesion strengths ( τ 50 ) than their non-invasive counterparts, HPL1D and MCF-7. Detachment dynamics inversely correlated with cell invasion potentials. A theoretical model, based on τ 50 values and the distribution of cell areas on substrates, provided good fits to results from de-adhesion experiments. Quantification of cell tractions, using the Reg-FTTC method on 10 kPa polyacrylamide gels, showed highest values for invasive, MDAMB-231 and A549, cells compared to non-invasive cells. Immunofluorescence studies show differences in vinculin distributions; non-invasive cells have distinct vinculin puncta, whereas invasive cells have more dispersed distributions. The cytoskeleton in non-invasive cells was devoid of well-developed stress fibers, and had thicker cortical actin bundles in the boundary. Fluorescence intensity of actin was significantly lower in invasive cells as compared to non invasive cells. These correlations in adhesion strengths and traction stresses with cell invasiveness may be useful in cancer diagnostics and other pathologies featuring mis-regulation in adhesion.