NIH Public Access: Shapes of Red Blood Cells: Comparison of 3D Confocal Images with the Bilayer-Couple Model

Khaled Khairy, JiJinn Foo, and Jonathon Howard, Cell Mol Bioeng 1; 1(2-3): 173–181, 2010

Cells and organelles are shaped by the chemical and physical forces that bend cell membranes. Thehuman red blood cell (RBC) is a model system for studying how such forces determine cellmorphology. It is thought that RBCs, which are typically biconcave discoids, take the shape thatminimizes their membrane-bending energies, subject to the constraints of fixed area and volume.However, recently it has been hypothesized that shear elasticity arising from the membraneassociatedcytoskeleton (MS) is necessary to account for shapes of real RBCs, especially ones withhighly curved features such as echinocytes. In this work we tested this hypothesis by following RBCshape changes using spherical harmonic series expansions of theoretical cell surfaces and thoseestimated from 3D confocal microscopy images of live cells. We found (i) quantitative agreementbetween shapes obtained from the theoretical model including the MS and real cells, (ii) thatweakening the MS, by using urea (which denatures spectrin), leads to the theoretically predictedgradual decrease in spicule number of echinocytes, (iii) that the theory predicts that the MS is essentialfor stabilizing the discocyte morphology against changes in lipid composition, and that without it,the shape would default to the elliptocyte (a biconcave ellipsoid), (iv) that we were able to induceRBCs to adopt the predicted elliptocyte morphology by treating healthy discocytes with urea. Thelatter observation is consistent with the known connection between the blood disease hereditaryelliptocytosis and spectrin mutations that weaken the cell cortex. We conclude that while thediscocyte, in absence of shear, is indeed a minimum energy shape, its stabilization in healthy RBCsrequires the MS, and that elliptocytosis can be explained based on purely mechanical considerations.

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