Revealing the dynamic adsorption and diffusion of peptide amphiphile on supported lipid bilayer by single molecule experiment and simulation

Abstract

Dynamic adsorption and diffusion of peptide amphiphiles (PAs) with different numbers of alkyl tails on supported lipid bilayers (SLBs) were investigated by single molecule tracking experiment and molecule dynamic simulation. Experimental results show two distinct populations of PAs with different residence time. Residence time of adsorbed PAs increases with the increase of the alkyl tails, whereas diffusion coefficient monotonically decreases with rising the number of alkyl tails and also decreases with increasing the mobility of SLBs. All-atom molecule dynamic simulation results prove that the adsorption and diffusion of PAs on SLB surface are mainly determined by interactions between PAs and SLBs and also the intrinsic mobility of PAs in aqueous solution. The electrostatic interactions and the mobility of PAs are two dominated but contradictory coefficients for the adsorption and diffusion of PAs. By increasing the alkyl tails, the mobility of PAs decreases while the electrostatic property does not change significantly, resulting in the increase of residence time and decrease of diffusivity of PAs. Additionally, for the PAs with large number of alkyl tails (≥ 3 alkyl tails), steric hindrance of alkyl tails leads to the decrease of adsorption probability of PAs on SLB surface. These findings lay the groundwork for guiding the design of PAs with high cell affinity, potentially useful for efficient drug delivery.

Keywords: Adsorption; All-atom molecule dynamic simulation; Diffusion; Peptide amphiphile; Single molecule tracking.