Atomistic analysis of the effect of cholesterol on cancerous membrane protein system: unfolding and associated resistance stresses under strain

The low-cholesterol cancerous environment can affect the biophysical behaviour of transmembrane proteins. It is difficult to experiment and measure the dynamics of membrane protein systems when cholesterol concentration is decreasing. In this work, atomistic approach is adopted to investigate the transmembrane protein behaviour during lipid-bilayer separation under strain at different cholesterol concentrations. Finding shows that the decreasing cholesterol across membrane protein system leads to an increase in area-per-lipid and average tilt angle by 6.4% and 62.6%, respectively with decreased order parameter. This observation indicates that the decreased cholesterol concentration in a cancerous environment hinders the bonding and compactness of membrane protein system. Stretching and unfolding of protein were observed during bilayer separation and the resistance stresses decreased by 68.01% for decreasing cholesterol. The cholesterol molecules observed to be bonded with proteins. The investigation revealed that the cholesterol is an important constituent of membrane that impedes the diffusion and resist the detachment of protein at high concentration. Thereby, the transmembrane proteins can retain end terminals positions across the membrane and resist functional failure. This study showed that decreased cholesterol concentration causes significant changes in the biophysical behaviour of the membrane protein system that could trigger the mechanosensitivity of transmembrane proteins under mechanical perturbation.

Automated summary

Decreasing cholesterol concentration affects the biophysical behavior of transmembrane proteins. The study found that lowering cholesterol leads to increased area-per-lipid and average tilt angle, as well as decreased order parameter in the protein system. The decreased cholesterol concentration impedes bonding and compactness of membrane proteins, but also helps retain protein positions and resist functional failure.