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Substrate rigidity dictates phenotype, survival, and mechanics of primary human osteosarcoma cells

Mylonaki Eleni, Dailiana, Z., Trepat, X., Lagoudakis Michael

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Summary

Chemical cues and physical forces tightlycontrol the milieu where a cell is born, survives, andfinally dies. Of the physical forces, tissue rigidity isknown to direct cell fate. Nonetheless, malignanttumors drastically alter the local physiological tissuerigidity. Our aim was to determine the functionalchanges of cells derived from an osteosarcoma, avery stiff malignant formation, to substrates of varyingrigidity. Cells extracted from a human femoralosteosarcoma were exposed to collagen I-coatedpolyacrylamide substrates mimicking the rigidity ofbrain (1 kPa), connective tissue (7 kPa), and collagenousbone (55 kPa). Glass was used as a controlsubstrate. Osteosarcoma cells occupied the smallestarea and were rounder when on the compliant 1 kPasubstrate compared to the stiffer substrates. Additionally,cell apoptosis, as assessed by Annexin Vstaining, and total death rate were significantly increasedon the more compliant substrates of 1 and 7kPa. Finally, as computed via a Fourier transformalgorithm, cells exerted greater traction forces on therigid 55 kPa substratum and less on the more compliant7 and 1 kPa substrates. Taken together, thesedata suggest that osteosarcoma cells survive andfunction more efficiently on substrates mechanicallycloser to their native microenvironment.

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