Jiang Dongping, Lin Yu-Chien, Shin Sungmin, Choe Younghwan, Cho Nam-Joon
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798 Singapore.
Centre for Cross Economy Global, Nanyang Technological University, 60 Nanyang Drive, SBS-01s-50, 637551 Singapore.
J Phys Chem B. 2025 Jun 19;129(24):5976-5988. doi: 10.1021/acs.jpcb.5c00994. Epub 2025 May 19.
The interplay between fatty acids (FAs) and lipid membranes under varying pH conditions is important for deciphering fundamental cellular processes and advancing the design of responsive applications. Endowed with membrane incorporation, fatty acids (FAs) can induce curvature on membranes, resulting in alterations in fluidity, permeability, and stability. Despite the wide amount of research on membrane effects induced by FAs, the pH effect on their interaction behaviors remained unclear. Considering the varying pH environments in vivo, the study investigates how pH modulates the aggregation behavior of oleic acid (OA) and its subsequent interactions with lipid membranes. First, the critical aggregation concentration (CAC) was measured to determine the condition when aggregates formed. Less ordered aggregates with a lower zeta potential were observed under elevated pH conditions. These aggregates were further introduced to lipid membranes to evaluate the corresponding membrane responses using a QCM-D and fluorescence microscopy. pH shifts dramatically alter the OA protonation states of their headgroups, driving their insertion, orientation, and aggregation within membranes. Specifically, under lower pH levels, OA demonstrated an incorporation behavior into the membrane structure with increased membrane viscoelasticity, while disturbance of membrane structural integrity was observed under elevated pH levels. A transition from flatter budding protrusions to elongated tubes on the membrane was observed for incorporated OA, primarily owing to the increasing deprotonation degree that resulted in a change in the packing parameter. A stronger impact on cell viability at higher pH levels verified the membrane disruption behaviors. These findings elucidated that the protonation states of OA headgroups critically influence their membrane affinity and packing behavior, offering new perspectives for understanding membrane biophysics and designing pH-responsive delivery systems.
在不同pH条件下，脂肪酸（FAs）与脂质膜之间的相互作用对于解读基本细胞过程和推动响应性应用的设计至关重要。脂肪酸（FAs）能够融入膜中，可诱导膜产生曲率，从而导致流动性、渗透性和稳定性发生改变。尽管对脂肪酸诱导的膜效应已有大量研究，但pH对其相互作用行为的影响仍不明确。考虑到体内pH环境的变化，本研究探讨了pH如何调节油酸（OA）的聚集行为及其随后与脂质膜的相互作用。首先，测量临界聚集浓度（CAC）以确定聚集体形成的条件。在较高pH条件下观察到具有较低zeta电位的无序聚集体。将这些聚集体进一步引入脂质膜，使用石英晶体微天平（QCM-D）和荧光显微镜评估相应的膜响应。pH的变化会显著改变OA头基的质子化状态，驱动它们在膜内的插入、取向和聚集。具体而言，在较低pH水平下，OA表现出融入膜结构的行为，膜的粘弹性增加，而在较高pH水平下则观察到膜结构完整性受到干扰。对于融入的OA，观察到膜上从较扁平的芽状突起向细长管的转变，这主要是由于去质子化程度增加导致堆积参数发生变化。在较高pH水平下对细胞活力有更强的影响，证实了膜破坏行为。这些发现阐明了OA头基的质子化状态对其膜亲和力和堆积行为有至关重要的影响，为理解膜生物物理学和设计pH响应性递送系统提供了新的视角。
