How Cell-Penetrating Peptides Behave Differently from Pore-Forming Peptides: Structure and Stability of Induced Transmembrane Pores

• DOI: 10.1021/jacs.3c08014
• Publication Date: 2023-11-22T02:27:31Z
• Authors: Haleh Alimohamadi; Jaime de Anda; Michelle W. Lee; Nathan W. Schmidt; Taraknath Mandal; Gerard C. L. Wong
• Keywords: X-Ray Diffraction; Lipid Bilayers; Scattering, Small Angle; Cell-Penetrating Peptides; Amino Acid Sequence

Peptide-induced transmembrane pore formation is commonplace in biology. Examples of pores include formed by antimicrobial peptides (AMPs) and cell-penetrating (CPPs) bacterial membranes eukaryotic membranes, respectively. In general, however, depends on peptide sequences, lipid compositions, intensive thermodynamic variables difficult to observe directly under realistic solution conditions, with structures that are challenging measure directly. contrast, the structure phase behavior peptide-lipid systems relatively straightforward map out experimentally for a broad range conditions. Cubic phases often observed involving pore-forming peptides; it not clear how structural tendency induce negative Gaussian curvature (NGC) such quantitatively related geometry biological pores. Here, we leverage theory anisotropic inclusions devise facile method estimate sizes from geometric parameters cubic measured small-angle X-ray scattering (SAXS) show estimates compare well known sizes. Moreover, our model suggests although AMPs can stable CPPs highly labile, consistent atomistic simulations.