The mechanical properties of biogenic membranous compartments are thought to be relevant in numerous biological processes; however, their quantitative measurement remains challenging for most of the already available Force Spectroscopy (FS)-based techniques. In particular, the debate on the mechanics of lipid nanovesicles and on the interpretation of their mechanical response to an applied force is still open. This is mostly due to the current lack of a unified model being able to describe the mechanical response of gel and fluid phase lipid vesicles and to disentangle the contributions of membrane rigidity and luminal pressure. In this framework, we herein propose a simple model in which the contributions of membrane rigidity and luminal pressure to the overall vesicle stiffness are described as a series of springs; this approach allows estimating the two contributions for both gel and fluid phase liposomes. Atomic Force Microscopy-based FS (AFM-FS), performed on both vesicles and Supported Lipid Bilayers (SLBs), is exploited for obtaining all the parameters involved in the model. Moreover, the use of coarse-grained full-scale molecular dynamics simulations allowed for better understanding the differences in the mechanical responses of gel and fluid phase bilayers and supported the experimental findings. Results suggest that the pressure contribution is similar among all the probed vesicle types; however, it plays a dominant role in the mechanical response of lipid nanovesicles presenting a fluid phase membrane, while its contribution becomes comparable to the one of membrane rigidity in nanovesicles with a gel phase lipid membrane. The herein presented results offer a simple way to quantify two of the most important parameters in vesicular nanomechanics, and as such represent a first step towards a currently unavailable, unified model for the mechanical response of gel and fluid phase lipid nanovesicles.

中文翻译：

---

流体和凝胶相脂质纳米囊泡的刚度：加权膜弯曲模量和管腔加压的贡献

生物膜隔室的机械特性被认为与许多生物过程有关。然而，对于大多数已经可用的基于力谱 (FS) 的技术而言，它们的定量测量仍然具有挑战性。特别是，关于脂质纳米囊泡的力学及其对施加的力的机械响应的解释的争论仍然存在。这主要是由于目前缺乏能够描述凝胶和流体相脂质囊泡的机械响应并解开膜刚度和管腔压力的贡献的统一模型。在这个框架中，我们在这里提出了一个简单的模型，其中膜刚度和管腔压力对整体囊泡刚度的贡献被描述为一系列弹簧；这种方法允许估计凝胶和流体相脂质体的两个贡献。基于原子力显微镜的 FS (AFM-FS) 在囊泡和支持的脂质双层 (SLB) 上执行，用于获取模型中涉及的所有参数。此外，使用粗粒度的全尺寸分子动力学模拟可以更好地理解凝胶和流体相双层机械响应的差异，并支持实验结果。结果表明，所有探测的囊泡类型之间的压力贡献相似；然而，它在呈现流体相膜的脂质纳米囊泡的机械响应中起主导作用，而其贡献与具有凝胶相脂质膜的纳米囊泡中的膜刚度相当。