Peptide sequences containing acidic and basic residues could potentially have their net charges modulated by bulk pH with a possible influence on their lytic activity in lipid vesicles. The present study reports on a biophysical investigation of these modulatory effects on the synthetic mastoparan-like peptide L1A (IDGLKAIWKKVADLLKNT-NH2). At pH 10.0 L1A was 6 times more efficient in lysing large anionic (1-palmitoyl-oleoyl-sn-glycero-3-phosphocholine (POPC):1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG)/(8:2)) unilamellar vesicles (LUVs) than at pH 4.0. Despite the reduction of 60% in the L1A net charge in basic pH its affinity for this vesicle was almost insensitive to pH. On the other hand, L1A insertion into monolayers was dramatically influenced by subphase condition, showing that, in the neutral and basic subphases, the peptide induced surface pressure changes that surpassed the membrane lateral pressure, being able to destabilize a bilayer structure. In addition, in the basic subphase, visualization of the compression isotherms of co-spread 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC):POPG (8:2) + 4.8 mol% L1A showed that the peptide induced significant changes in solid lipid domains, indicating its capability in perturbing lipid-packing. An insight into L1A lytic activity was also obtained in giant unilamellar vesicles (GUVs) using phase contrast microscopy. The suppression of L1A lytic activity at acidic pH is in keeping with its lower insertion capability and ability to disturb the lipid monolayer. The lytic activity observed under neutral and basic conditions showed a quick and stochastic leakage following a lag-time. The permeability and the leakage-time averaged over at least 14 single GUVs were dependent on the bulk condition. At basic pH, permeability is higher and quicker than in a neutral medium in good accordance with the lipid-packing perturbation.

含有酸性和碱性残基的肽序列可能会通过整体pH值调节其净电荷，并可能影响其在脂质囊泡中的裂解活性。本研究报告了这些对合成的类脂蛋白样肽L1A（IDGLKAIWKKVADLLKNT-NH2）的调节作用的生物物理研究。在10.0的pH值下，L1A裂解大型阴离子（1-棕榈酰基-油酰基-sn-甘油-3-磷酸胆碱（POPC）：1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸甘油（POPG）/ （8：2））的单层囊泡（LUV）的pH值低于4.0。尽管在碱性pH中L1A净电荷减少了60％，但其对这种囊泡的亲和力几乎对pH不敏感。另一方面，L1A插入单层受到子相条件的显着影响，表明在中性和基本子相中，肽诱导的表面压力变化超过膜的侧向压力，从而使双层结构不稳定。此外，在基本子阶段中，共扩散的1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）：POPG（8：2）+ 4.8 mol％L1A的压缩等温线的可视化表明，肽诱导固体脂质结构域的显着变化，表明其干扰脂质堆积的能力。还使用相差显微镜在巨型单层囊泡（GUV）中获得了对L1A裂解活性的了解。L1A裂解活性在酸性pH下的抑制与其较低的插入能力和干扰脂质单层的能力保持一致。在中性和碱性条件下观察到的裂解活性在滞后时间后显示出快速而随机的泄漏。至少14个单一GUV的平均渗透率和泄漏时间取决于整体条件。在碱性pH值下，渗透性比中性介质中的渗透性更高和更快，这与脂质堆积的扰动非常吻合。