Abstract: Membrane protein binding and unbinding processes stand out as a reliable means of intercellular adhesion-based signal transduction. Based Helfrich’s elastic membrane model [1], we attempt to shed light on the subtle effects of thermal membrane undulations on equilibrium binding and domain formation of membrane-anchored proteins maintaining a cellular adhesion zone. Devising a statistical mechanics approach supported by Monte-Carlo (MC) simulations [2], we find that successful receptor-ligand binding locally encourages the establishment of proximal bound complexes. This mechanistic picture entails a local cooperative law of mass action for receptor-ligand interactions in membrane adhesion zones [3]. On the other hand, we present an extension of this adhesion model reminiscent of the immunological synapse containing two pairs of receptors and ligands – e.g. pMHC-TCR and LFA/ICAM – differing in size and binding affinity. In such a setting, stable domain formation is possible. We corroborate the existence of a critical point [4] of domain formation caused by membrane shape fluctuations and use classical nucleation theory to derive stability criteria for co-existing micro-domains. In this context, we show that membrane undulations increase the energetic penalty for domain formation by modulating line tension scaling near the critical point [5]. These thermally stable micro-domains may merge to macroscopic domains conducive to immunological synapse formation.

References:

[1] TR Weikl, M Asfaw, H Krobath, et al. Soft Matter, 2009, 5(17):3213-3224.

[2] H Krobath, GJ Schütz, R Lipowsky, TR Weikl. Europhys Lett., 2007, 78:38003

[3] H Krobath, B Różycki, R Lipowsky, TR Weikl. Soft Matter, 2009, 5:3354-3361.

[4] M Asfaw, B Różycki, R Lipowsky, TR Weikl. Europhys Lett., 2006, 76(4):703-709.

[5] H Krobath, B Różycki, R Lipowsky, TR Weikl. PLoS ONE, 2011, 6(8): e23284.