Coarse-grained modelling of blood cell mechanics

  • Paul Appshaw

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


This thesis concerns development of mechanically realistic in silico representations of human blood cells using coarse-grained molecular dynamics (CGMD), ultimately building a new model for a lymphocyte-class white blood cell (WBC). This development is approached successively, evaluated through simulation of experimental testing methods common to past in vitro studies on blood cell mechanics. Considering both their biophysical simplicity and the extensive associated literature, the red blood cell (RBC) is first considered. As a foundation, I thus used the CGMD RBC model of Fu et al. [Lennard-Jones type pair-potential method for coarse-grained lipid bilayer membrane simulations in LAMMPS, Fu et al., Comput. Phys. Commun., 210, 193-203 (2017)]. Chapter 3 establishes implementation of this model, and in silico implementations of the three chosen testing methods. In doing so, the first quantitative assessment of the "miniature cell" approach is conducted - being the down-scaling of the physical cell size to make feasible simulation times, as was done in the original article presenting the model.

The RBC model is then used as a foundation from which to develop a new whole-cell WBC lymphocyte model. This is approached sequentially. Firstly (Chapter 4), the morphology and mechanics relevant to the existing RBC model are adapted to those of a lymphocyte. As such, a quasi-spherical morphology is induced, and elastic membrane-associated parameters brought in line with the literature on isolated lymphocytes in vitro. A semi-rigid nucleus is then added to the cell interior, again parameterised to produce elastic properties consistent with the literature. These developments produce a cell having macroscopic mechanical properties much more consistent with a WBC, with an "optimal" parameterisation established.

After the membrane and nucleus, the entity most influential to the mechanics of nucleated cells (such as WBC) is their complex intracellular actin-based cytoskeleton (CSK). Therefore, Chapter 5 attempts to represent such a system within our new lymphocyte model. This is approached in three successive stages, assessed against recognised CSK mechanical properties, in particular those also common to soft glassy materials. As such, a novel CSK representation is developed, inspired as a discretisation of soft glassy rheology (SGR). It is proposed that the resulting system has characteristics comparable to having undergone a glass-like transition, as relatable to a real CSK. Therefore, the resulting lymphocyte model may lay a foundation for future development towards mechanically accurate representations of other cells - in particular, a circulating tumour cell.
Date of Award5 Dec 2023
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorAnnela M Seddon (Supervisor) & Simon Hanna (Supervisor)

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