Elastic deformation and failure in protein filament bundles: Atomistic simulations and coarse-grained modeling

Abstract

The synthetic peptide RAD16-II has shown promise in tissue engineering and drug delivery. It has been studied as a vehicle for cell delivery and controlled release of IGF-1 to repair infarcted cardiac tissue, and as a scaffold to promote capillary formation for an in vitro model of angiogenesis. The structure of RAD16-II is hierarchical, with monomers forming long β-sheets that pair together to form filaments; filaments form bundles approximately 30-60 nm in diameter; branching networks of filament bundles form macroscopic gels. We investigate the mechanics of shearing between the two β-sheets constituting one filament, and between cohered filaments of RAD16-II. This shear loading is found in filament bundle bending or in tensile loading of fibers composed of partial-length filaments. Molecular dynamics simulations show that time to failure is a stochastic function of applied shear stress, and that for a given loading time behavior is elastic for sufficiently small shear loads. We propose a coarse-grained model based on Langevin dynamics that matches molecular dynamics results and facilities extending simulations in space and time. The model treats a filament as an elastic string of particles, each having potential energy that is a periodic function of its position relative to the neighboring filament. With insight from these simulations, we discuss strategies for strengthening RAD16-II and similar materials.

Visualizing the Histotripsy Process: Bubble Cloud–Cancer Cell Interactions in a Tissue-Mimicking Environment

“…However, the process of histotripsy tissue fractionation has not yet been visualized on a cellular level or on the time scales at which the damage is achieved. Additionally, while RBC phantoms are a good model to visualize the area ablated by histotripsy, the model is limited to suspended RBCs that fractionate at significantly smaller deformations than adherent cells attached to an extracellular matrix (ECM) (Barbee 2005; Hammond and Kamm 2008; Kilinc et al 2009; Ofek et al 2010). Therefore, the question remains as to how histotripsy fractionates adherent cells within an ECM that can undergo much larger deformations before rupture (Barbee 2005; Hammond and Kamm 2008; Kilinc et al 2009; Ofek et al 2010).…”

Mechanical characterization of self‐assembling peptide hydrogels by microindentation

“…However, as we noted in previous work,42 when the cellular solids model is applied to peptide gels, it overestimates bulk stiffness by a factor of about 1000. In that study, we asked whether free slip between bundled filaments could account for this discrepancy and examined the shear forces between sliding filaments using molecular dynamics simulations and coarse‐grained modeling.…”

“…Work has been done to systematically vary the peptide sequence to examine whether the bulk modulus changes with various factors, including peptide length40 and the period of repetition of the pattern of charge in the oligopeptide sequence 7. Molecular dynamics simulations have been used to observe the mechanical properties of individual filaments41 and the strength of interactions between filaments,42 and experimental techniques are available to measure the bending stiffness (via persistence length) of filaments43 and the mechanical properties of bulk gels 5, 7…”

“…With clear structural data lacking, it has sometimes been assumed that filaments align in parallel into dense bundles of many filaments,5, 42, 45 A gel formed from such dense bundles lends itself to cellular solids analysis, in which a typical unit cell is considered as a framework of elastic (Euler‐Bernouli) beams, and simple scaling arguments relate loads and displacements of a unit cell to bulk stress and strain 46, 47…”

Molecular simulation studies on microstructure of phospholipid nano-carrier for hydrophobic drug delivery

“…Each bead represents a group of atoms or a volume of fluid that is large on the atomistic scale but still macroscopically small. 30 Dynamics evolution of the beads is governed by Newton's second law. Groot and Warren 31 32 established the relationship between the repulsive parameter a ii and the FloryHuggins parameters ij .…”