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Non-uniform distribution of myosin-mediated forces governs red blood cell curvature through tension modulation

By Haleh Alimohamadi, Alyson S Smith, Velia M Fowler, Padmini Rangamani

Posted 12 Jun 2019
bioRxiv DOI: 10.1101/668582

The biconcave disk shape of the mammalian red blood cell (RBC) is unique to the RBC and is vital for its circulatory function. Recent experiments have demonstrated that the biconcave shape of the RBC relies not only on the physical properties of the membrane but also depends on the molecular constituents of the membrane cytoskeleton, including the contractile activity of the nonmuscle myosin IIA (NMIIA) motor protein. Here, we use the classical Helfrich model for the RBC membrane and incorporate heterogeneous force distributions along the membrane to mimic the contractile activity of NMIIA. We find that the biconcave shape of the RBC depends on the ratio of forces per unit volume in the dimple and donut regions of the RBC. Experimental measurements of NMIIA densities at the dimple and donut validate our prediction that (a) membrane forces must be non-uniform along the RBC membrane and (b) the force density must be larger in the dimple region than the donut region to produce the observed membrane curvatures. Furthermore, we find that the tension of the RBC membrane plays an important role in regulating this force-shape landscape. Our findings of heterogeneous force distributions on the plasma membrane for RBC shape maintenance have implications for shape maintenance of many cell types.

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