Influence of Alcohols on the Bending Rigidity and the Thickness of Phospholipid Membranes: The Role of Chain Length Mismatch

Alcohols influence the shape of the cells. To elucidate this phenomenon and understand the influence of alcohols on the mechanical properties of cell membranes such as bending rigidity, it is essential to investigate their effects on lipid bilayers. In this study, we explored the impact of short- and medium-chain alcohols on the bending rigidity and thickness of 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphocholine (DMPC) bilayers in the fluid phase. We employed various techniques, including vesicle fluctuation analysis, small-angle X-ray scattering, and differential scanning calorimetry. Experimental observations were further validated and interpreted using atomistic molecular dynamics simulations. Our results demonstrate that alcohols ranging from ethanol to octanol reduce the main phase transition temperature (<i>T</i>_m), bending rigidity (κ), and thickness of the bilayer (<i>D</i>_HH). Decanol and dodecanol, on the other hand, increase <i>T</i>_m without significantly affecting κ and the bilayer thickness. Our study conclusively shows that alcohols shorter than decanol induce a negative chain length mismatch condition, leading to disorder and enhanced interdigitation in DMPC membranes, resulting in membrane thinning and softening. In contrast, decanol, whose chain length matches that of the lipid, enhances lipid chain order and reduces their interdigitation, resulting in no alteration in the bending rigidity and membrane thickness.