Browsing by Author "Shroff, Hari"

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    Controlling Curvature and Stiffness in Fibrous Environments Uncovers Force-Driven Processes and Phenotypes
    Hernandez Padilla, Christian (Virginia Tech, 2024-08-22)
    In recent decades science has become an increasingly multidisciplinary field in which the lines that used to divide starkly different fields have blurred or disappeared completely. This work is a compendium of different angles focused at exploring disease progression of cancer biology through the perspective of mechanical engineering. We explore cancer through a holistic approach considering mechanistic, physical, genetic biology, biochemical, and immune cells to explore how the interplay with fiber networks can expand our understanding. We explored the physical interplay with biological processes of fibroblastic cells and show how these are critically regulated by forces that alter their ability to coil depends on fiber curvature and adhesion strength; thus, showing how cellular processes are driven by the balances of mechanical forces. Conversely, not all cell types are driven by the same factors, where we report that the structural features of migratory DCs enable them to be less influenced by the differences in fiber diameters, contrasting drastically what we previously reported on the other cell lines. Finally developing a novel composite nanofiber platform, we reported how some cancer cells are mechanistically influenced by the architecture of a substrate and thus resulting in completely different migratory responses that we have associated with key regulatory genes and responding completely differently when in the presence of clinically relevant molecular therapies. Overall, we investigated cancer biology through stiffness gradients, geometric influence through biophysics on myoblasts, and immune cell migration forces as a strong indicator of cell behavior.
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    Experimental and theoretical model for the origin of coiling of cellular protrusions around fibers
    Sadhu, Raj Kumar; Hernandez-Padilla, Christian; Eisenbach, Samo Penič; Zhang, Lixia; Vishwasrao, Harshad D.; Behkam, Bahareh; Konstantopoulos, Konstantinos; Shroff, Hari; Iglič, Aleš; Peles, Elior; Nain, Amrinder S.; Gov, Nir S. (Nature Research, 2023-09-12)
    Protrusions at the leading-edge of a cell play an important role in sensing the extracellular cues during cellular spreading and motility. Recent studies provided indications that these protrusions wrap (coil) around the extracellular fibers. However, the physics of this coiling process, and the mechanisms that drive it, are not well understood. We present a combined theoretical and experimental study of the coiling of cellular protrusions on fibers of different geometry. Our theoretical model describes membrane protrusions that are produced by curved membrane proteins that recruit the protrusive forces of actin polymerization, and identifies the role of bending and adhesion energies in orienting the leading-edges of the protrusions along the azimuthal (coiling) direction. Our model predicts that the cell’s leading-edge coils on fibers with circular cross-section (above some critical radius), but the coiling ceases for flattened fibers of highly elliptical cross-section. These predictions are verified by 3D visualization and quantitation of coiling on suspended fibers using Dual- View light-sheet microscopy (diSPIM). Overall, we provide a theoretical framework, supported by experiments, which explains the physical origin of the coiling phenomenon.