Single Cell Mechanics in Disease Progression

Figures

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  FIGURE 1. Mechanical forces transmitted from the ECM and cell–cell adhesions to the nucleus. Cells transmit distinct mechanical forces via ECM adhesion and cell–cell junctions. Yellow arrows denote tensile forces, green arrows indicate compressive forces, and blue arrows represent traction forces. At the cell–ECM interface, actomyosin‐generated traction forces are transmitted to the substrate via integrin‐based focal adhesions. These forces are opposed by ECM resistance and transmitted inward through the actin cytoskeleton toward the nucleus. At cell–cell junctions, actomyosin contractility in adjacent cells generates intercellular tensile forces concentrated at adherens junctions, where E‐cadherin complexes mechanically couple neighboring cells. Opposing contractile forces between adjacent cells generate localized compressive stresses in the junctional region and surrounding cytoplasm. Mechanical signals are transmitted to the nucleus via the LINC complex, connecting the cytoskeleton to the nuclear lamina. Actin filaments primarily transmit tensile forces to the nucleus, while intermediate filaments dissipate mechanical loads and provide structural stabilization by buffering compressive…

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  FIGURE 2. Quantification of cell–substrate adhesion and force generation across molecular and cellular scales. (A) Conceptual schematic of an RWG sensor. The RWG sensor couples incident light at a specific wavelength into a guided wave mode via a periodic diffraction grating on the waveguide surface. At resonance, an evanescent field (∼150 nm penetration depth) forms above the waveguide surface and responds sensitively to local refractive index changes near the sensor interface. Cell adhesion via integrin–RGD interactions alters the effective refractive index, producing a measurable shift in resonant wavelength. This optical shift enables high‐resolution readout of adhesion strength, where yellow indicates strong adhesion and blue denotes weak adhesion. Adapted with permission [27] 2021, Scientific Reports. (B) Conceptual schematic of TGT. Mechanosensitive DNA constructs activate when applied tension exceeds a defined rupture threshold. Double‐stranded DNA serves as a force‐sensitive tether; ligand binding to integrins applies mechanical load to the DNA linker. Depending on force magnitude, the tether ruptures or remains intact, allowing indirect quantification of cellular traction forces.…

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  FIGURE 3. Quantification of mechanical forces transmitted across cell–cell adhesions. (A) Conceptual schematic of lipid‐modified DNA molecular tension probes. A DNA hairpin with a defined force threshold is flanked by a fluorophore (FAM) and a quencher (Eclipse) at opposite ends. Lipid modification anchors the probe in the cell membrane, while a protein G linker enables selective binding to E‐cadherin. Tensile force generated at cell–cell adhesions unfolds the hairpin, separating FAM and quencher and restoring fluorescence. A Cy5 reference signal enables normalization independent of tension‐dependent fluorescence changes. Adapted with permission [80] 2023, Frontiers in Cell and Developmental Biology. (B) Conceptual schematic of TFM. Two layers of fluorescent beads are embedded within an elastic substrate. One layer serves as a fiduciary reference at the glass–elastomer interface, while the second layer tracks cell‐induced deformation. Lower image: a traction stress map. Bead displacements measured before and after cell detachment are used to calculate traction stresses using the Fourier transform TFM. Blue and red arrows indicate local in‐plane traction stress vectors (σz) exerted by cells…

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