An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts.

Autor: Tantiwong C; School of Biological Sciences, University of Reading, Reading, UK.; Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands., Dunster JL; School of Biological Sciences, University of Reading, Reading, UK., Cavill R; Department of Data Science and Knowledge Engineering, Maastricht University, Maastricht, The Netherlands., Tomlinson MG; School of Biosciences, University of Birmingham, Birmingham, UK., Wierling C; Alacris Theranostics GmbH, Berlin, Germany., Heemskerk JWM; Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands.; Synapse Research Institute, Maastricht, The Netherlands., Gibbins JM; School of Biological Sciences, University of Reading, Reading, UK. j.m.gibbins@reading.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Mar 08; Vol. 13 (1), pp. 3906. Date of Electronic Publication: 2023 Mar 08.
DOI: 10.1038/s41598-023-30884-6
Abstrakt: Receptor diffusion plays an essential role in cellular signalling via the plasma membrane microenvironment and receptor interactions, but the regulation is not well understood. To aid in understanding of the key determinants of receptor diffusion and signalling, we developed agent-based models (ABMs) to explore the extent of dimerisation of the platelet- and megakaryocyte-specific receptor for collagen glycoprotein VI (GPVI). This approach assessed the importance of glycolipid enriched raft-like domains within the plasma membrane that lower receptor diffusivity. Our model simulations demonstrated that GPVI dimers preferentially concentrate in confined domains and, if diffusivity within domains is decreased relative to outside of domains, dimerisation rates are increased. While an increased amount of confined domains resulted in further dimerisation, merging of domains, which may occur upon membrane rearrangements, was without effect. Modelling of the proportion of the cell membrane which constitutes lipid rafts indicated that dimerisation levels could not be explained by these alone. Crowding of receptors by other membrane proteins was also an important determinant of GPVI dimerisation. Together, these results demonstrate the value of ABM approaches in exploring the interactions on a cell surface, guiding the experimentation for new therapeutic avenues.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje