Water ordering controls the dynamic equilibrium of micelle–fibre formation in self-assembly of peptide amphiphiles

Abstract

Understanding the role of water in governing the kinetics of the self-assembly processes of amphiphilic peptides remains elusive. Here, we use a multistage atomistic-coarse-grained approach, complemented by circular dichroism/infrared spectroscopy and dynamic light scattering experiments to highlight the dual nature of water in driving the self-assembly of peptide amphiphiles (PAs). We show computationally that water cage formation and breakage near the hydrophobic groups control the fusion dynamics and aggregation of PAs in the micellar stage. Simulations also suggest that enhanced structural ordering of vicinal water near the hydrophilic amino acids shifts the equilibrium towards the fibre phase and stimulates structure and order during the PA assembly into nanofibres. Experiments validate our simulation findings; the measured infrared O–H bond stretching frequency is reminiscent of an ice-like bond which suggests that the solvated water becomes increasingly ordered with time in the assembled peptide network, thus shedding light on the role of water in a self-assembly process.

Molecular simulations of self-assembling bio-inspired supramolecular systems and their connection to experiments

“…Other regions in the IR spectrum can also help in interpreting the dynamics of nanostructure as shown by Deshmukh et al for the water OH stretch region. 125 Vibrational spectra of both bulk water and water molecules close to the PA nanofibers were calculated by Fourier transforming of the atomic velocity autocorrelation function obtained from the MD simulation trajectories. This showed much more ordered water molecules in proximity to (especially hydrophilic) PA groups, which was experimentally validated by comparing PA assembly kinetics by IR and CD experiments in H 2 O and D 2 O.…”

Development of transferable coarse-grained models of amino acids

“…24,29,30 Research has also suggested that water ordering near the comparatively hydrophilic peptide portion of a PA provides structure to the PAs and thereby facilitates fiber formation-insights gleaned from combined AA and CG MD studies supported by experimental validation. 4 Altogether, the particular stable form (e.g. micelle, fiber, tube) of different PA self-assembled structures results from the particular strengths of and interplay between van der Waals forces, hydrogen bonding, and electrostatic interactions among the chemical constituents of the PAs and their surroundings.…”

“…shown in Figure 43; the CG model of the PA is shown in Figure 44. This is the PA that was simulated and synthesized in the study by Deshmukh, et al, 4 examining the role of water in PA self-assembly.…”

“…Additionally, research published using the Martini model to simulate the c16-AHL3K3-CO2H PA showed fiber formation within the first few microseconds, 4 although it is possible that such a time frame is not realistic. Considering that the 115% simulation shows clumping only of the hydrocarbon tails while the "varied" simulation shows more defined micelle formation, it becomes clear that it is important to consider the individual chemistry of each bead based on the atoms and functional group(s) the bead represents.…”

“…nuclear magnetic resonance (NMR), transmission infrared spectroscopy (IR), circular dichroism (CD), dynamic light scattering, and UV-vis absorption). 2,4 While these methodologies are indispensable to the investigation and elucidation of PA self-assembly structures and characteristics, they do not provide us with the ability to directly monitor the self-assembly process on the nanosecond and microsecond timescales. They also do not fully show individual PAs in this process and their interactions with other molecules in their environment like solvent water molecules.…”