Optical Tweezer Stretching of Miniature Coarse-Grained Red Blood Cells

Abstract

Due to the high computational cost of full-cell coarse-grained molecular dynamics modelling, being able to simulate "miniature" cells that effectively represent their full-sized counterparts would be highly advantageous. To accurately represent the morphological and elastic properties of a human red blood cell in silico, such a model is employed utilising the molecular dynamics package LAMMPS. The scale invariance of the model is first tested qualitatively by following the shape evolution of red blood cells of various diameters, then quantitatively by evaluating the membrane shear modulus from simulations of optical tweezer-style stretching. Cells of physical diameter of at least 0.5{micro}m were able to form the characteristic biconcave shape of human red blood cells, though smaller cells instead equilibrated to bowl-shaped stomatocytes. A positive correlation was found between the cell size and both magnitude of deformation from optical tweezer stretching and scaled shear modulus, indicating a lack of scale invariance in the models elastic response. However, the stable morphology and measured shear modulus of the 0.5 - 1.0{micro}m diameter cells are deemed close enough to past in vitro studies on human red blood cells for them to still offer valuable use in making simplified predictions of whole-cell mechanics. SIGNIFICANCEThe study tests the invariance of a coarse-grained molecular dynamics red blood cell (RBC) model to system scale, asking whether it is qualitatively and quantitatively viable to perform whole-cell simulations in "miniature". Simulating cells at a reduced scale greatly improves computational speed, making possible computational experiments that would otherwise be too computationally demanding. This facilitates the simulation of larger systems, both in number of whole-cells, and cells of greater structural complexity than the RBC. More generally, the accurate and efficient modelling of biological cells allows computational experimentation of real-world systems that would be very challenging or impossible to perform in vitro. Therefore, miniature-cell modelling could help both direct development in whole-cell modelling, and also developments in more widespread bio-physical studies.