Toward a Designable Extracellular Matrix: Molecular Dynamics Simulations of an Engineered Laminin-mimetic, Elastin-like Fusion Protein

TL;DR

This study uses molecular dynamics simulations to explore the temperature-dependent conformational behavior of a novel engineered laminin-elastin fusion protein, aiming to inform design of customizable extracellular matrices.

Contribution

It introduces a new laminin-elastin fusion protein design and characterizes its phase behavior through detailed molecular dynamics simulations.

Findings

Temperature influences secondary structure and hydration.

Emergence of β-sheet structures at physiological temperatures.

Insights into phase behavior of engineered ECM components.

Abstract

Native extracellular matrices (ECMs), such as those of the human brain and other neural tissues, exhibit networks of molecular interactions between specific matrix proteins and other tissue components. Guided by these naturally self-assembling supramolecular systems, we have designed a matrix-derived protein chimera that contains a laminin globular-like (LG) domain fused to an elastin-like polypeptide (ELP). All-atom, classical molecular dynamics simulations of our designed laminin-elastin fusion protein reveal temperature-dependent conformational changes, in terms of secondary structure composition, solvent accessible surface area, hydrogen bonding, and surface hydration. These properties illuminate the phase behavior of this fusion protein, via the emergence of $\beta$-sheet character in physiologically-relevant temperature ranges.