Membrane rheology and the interaction with peptides: Solid or fluid phases, liquid-disordered or liquid-ordered phases, hopanoids or sterols

CROSIO, MA; ALVARES, DAYANE S.; N. WILKE,

BERLIN

Congreso; Biomembrane days 2019; 2019

Cellular membranes regulate lateral diffusion of species, compartmentalization and permeability. Despite it has been shown that the organisms adapt the lipid composition of their membranes in order to mantain them in a mainly fluid state, several studies performed in plasma and internal membranes point to the existence of regions with different composition, leading to different mechanical properties. While proteins have been related with solid docks, sterols are accepted as liquid-ordered phase state inducers. Thus, the current model for membranes is a patchwork-like surface, with the different regions being highly variable both, in size and in time.On the other hand, molecules such as peptides that interact with membranes may have different affinities with different membrane compositions and rheology. As a consequence of the patchwork-like character of the membrane, membrane regions with a broad spectrum of properties are available for the interaction with a soluble peptide. Thus, it is important to know whether the peptide-membrane interaction depends on the membrane rheology, and also what happends with the different kind of membranes after that the interaction occurred.With this in mind, we studied the interaction and consequent effect of cationic peptides with membranes in gel and in fluid phase states. In this last membranes, the composition was varied in order to test liquid-disordered and liquid-ordered phase. Furthermore, liquid-ordered phases were induced with cholesterol or diplopterol, which is a sterol-surrogate hopanoid.The results indicate that the phase state is an important factor for peptide adsorption, incorporation into the membrane and consequent translocation across the membrane. Gel-like membranes showed a good interaction with a Cell Penetration Peptide (CPP). The CR9K peptide adsorbed, incorporated and crossed these membranes. However, membrane lysis was observed at low peptide concentrations. On the contrary, liquid-ordered membranes did not incorporate this peptide, but it remained adsorbed at the membrane surface. Finally, a good adsorption, penetration and translocation was observed when this peptide was added to membranes in a liquid-disordered phase state. After the CPP addition, membrane shape fluctuations increased and the membrane resistance upon curvature changes resulted weaker. Finally, a peptide with higher membrane affinity than CR9K was exposed to liquid-ordered membranes. MP1, a peptide with demonstrated antimicrobial character, was added to membranes with cholesterol or diplopterol. This peptide adsorbed, incorporated and crossed these membranes at low concentrations, and had lytic properties at high concentrations. However, the afinity and general interaction properties depended on which was the liquid-ordered phase inducer. Thus, besides the membrane phase state, there is an aditional regulation of the phenomena mediated by the membrane composition.