Self-entanglement of bovine serum albumin in shear flow: cumulative effects and irreversibility

Abstract

We perform Brownian dynamics simulations of shearinduced unfolding of bovine serum albumin. This protein was reported to unfold irreversibly in the shear flow. Using a coarse-grained model of a protein, we track the conformational changes induced by the flow and observe that after an extended exposure to shear albumin loses its ability to refold even when the flow has been turned off. Instead, it is trapped in a metastable state characterized by a large degree of selfentanglement which prevents the molecule from folding into the native conformation. This state becomes more populated with time, which can explain the cumulative effect of the shear observed in the experiments.

The uniqueness of flow in probing the aggregation behavior of clinically relevant antibodies

“…We have shown previously that flow‐induced aggregation of BSA occurs concurrently with the exposure of a cysteine residue, whose side‐chain is buried in the native state . Prediction of the extent of flow‐induced aggregation by in silico approaches may thus require a better understanding of the relationship between flow fields and local protein stabilization, the study of which is in its infancy …”

“… 59 Prediction of the extent of flow‐induced aggregation by in silico approaches may thus require a better understanding of the relationship between flow fields and local protein stabilization, the study of which is in its infancy. 67 …”

Physics inspired by living matter: dynamics, topology and functionality

“…-Functionality relates to the properties of engineered materials inspired by living matter, such as materials formed by colloidal and polymeric building blocks that can be tuned precisely to achieve macroscopic features such as non-wettability, thermal insulation, or structural coloration. Examples of these properties are given in the papers by Budek et al [8] as well as Chan and Carlson [9] in this issue.…”