University of Pennsylvania, Chemistry Department, 231 South 34th Street, Philadelphia, PA, 19104, USA.
Soft Matter. 2024 May 29;20(21):4291-4307. doi: 10.1039/d3sm01772a.
Lipid asymmetry - that is, a nonuniform lipid distribution between the leaflets of a bilayer - is a ubiquitous feature of biomembranes and is implicated in several cellular phenomena. Differential tension - that is, unequal lateral monolayer tensions comparing the leaflets of a bilayer- is closely associated with lipid asymmetry underlying these varied roles. Because differential tension is not directly measurable in combination with the fact that common methods to adjust this quantity grant only semi-quantitative control over it, a detailed understanding of lipid asymmetry and differential tension are impeded. To overcome these challenges, we leveraged reversible complexation of phospholipid by methyl-β-cyclodextrin (mbCD) to tune the direction and magnitude of lipid asymmetry in synthetic vesicles. Lipid asymmetry generated in our study induced (i) vesicle shape changes and (ii) gel-liquid phase coexistence in 1-component vesicles. By applying mass-action considerations to interpret our findings, we discuss how this approach provides access to phospholipid thermodynamic potentials in bilayers containing lipid asymmetry (which are coupled to the differential tension of a bilayer). Because lipid asymmetry yielded by our approach is (i) tunable and (ii) maintained over minute to hour timescales, we anticipate that this approach will be a valuable addition to the experimental toolbox for systematic investigation into the biophysical role(s) of lipid asymmetry (and differential tension).
脂质不对称性——即双层膜各叶层之间不均匀的脂质分布——是生物膜的普遍特征，并与多种细胞现象有关。差异张力——即比较双层膜各叶层的不等侧向单层张力——与这些不同作用下的脂质不对称密切相关。由于差异张力与普遍方法来调节该量的事实不能直接测量，而且只能对其进行半定量控制，因此对脂质不对称性和差异张力的详细理解受到阻碍。为了克服这些挑战，我们利用甲基-β-环糊精（mbCD）对磷脂的可逆络合来调节合成囊泡中脂质不对称的方向和幅度。我们的研究中产生的脂质不对称性诱导了（i）囊泡形状变化和（ii）1 组分囊泡中的凝胶-液相共存。通过应用质量作用考虑来解释我们的发现，我们讨论了这种方法如何提供对含有脂质不对称的双层膜中磷脂热力学势的访问（与双层膜的差异张力相关）。由于我们的方法产生的脂质不对称性（i）是可调的，（ii）可以维持数分钟到数小时的时间尺度，我们预计这种方法将成为系统研究脂质不对称性（和差异张力）的生物物理作用的实验工具箱的有价值补充。
