Modeling Pressure-Driven Transport of Proteins Through a Nanochannel

Abstract

Reducing the size of a nanofluidic channel not only creates new opportunities for high-precision manipulation of biological macromolecules, but also makes the performance of the entire nanofluidic system more susceptible to undesirable interactions between the transported biomolecules and the walls of the channel. In this manuscript, we report molecular dynamics simulations of a pressure-driven flow through a silica nanochannel that characterized, with atomic resolution, adsorption of a model protein to its surface. Although the simulated adsorption of the proteins was found to be nonspecific, it had a dramatic effect on the rate of the protein transport. To determine the relative strength of the protein–silica interactions in different adsorbed states, we simulated flow-induced desorption of the proteins from the silica surface. Our analysis of the protein conformations in the adsorbed states did not reveal any simple dependence of the adsorption strength on the size and composition of the protein–silica contact, suggesting that the heterogeneity of the silica surface may be a important factor.

Modeling the Interface between Biological and SyntheticComponents in Hybrid Nanosystems

“…It is known that without a protective coating of aminopropylsilane on silica or aminodecane on diamond surfaces, the antibodies can bind nonspecifically to both surfaces [61,29], losing their conformation and specific affinity to antigens. However, it is not known how the antibody proteins could interact with the substrates in the presence of the functionalization layer and how the functionalization layer degrades in solution.…”

“…To simplify the problem, we have studied protein-substrate interactions using individual amino acids in the place of an entire antibody protein. By focusing on the interactions of a substrate with individual amino acids we can estimate the interactions of a given protein with the substrate by looking at the amino-acid composition of the protein surface [29]. We have modeled the interaction of each substrate with amino acids from each of the representative types -positively charged, negatively charged, polar, nonpolar and aromatic -by creating new simulation systems with an amino acid in solution above a functionalized substrate.…”

“…It will be fascinating to watch the development of this art over the coming years. However, hybrid devices remain difficult to design because the interactions of the biomolecules and synthetic surfaces are often very strong, leading to the adsorption of biomolecules and the breakdown of the device [2,29].…”

“…When the interactions within these regions becomes significantly affect device function or behavior, such as the adsorption of solutes [37] that could lead to clogging of the device [18], the use of discrete methods like classical molecular dynamics (MD) becomes necessary. In my published work [38,39,29,37,40,41,42], I have used MD as a tool to describe the atomic-scale interactions driving the function of biomolecules and their interface with solid-state devices and sought to use it as a starting point to create new methods for modeling, designing, and optimizing these interactions.…”

“…This also prevents aggregation of the antibodies, as occurs in solution. Proteins, such as antibodies, tend to bind to inorganic surfaces strongly and nonspecifically [29]. To prevent adhesion of the antibodies to the substrates, the inorganic substrates are functionalized, or covalently coated, with a layer of protective molecules known as the functionalization layer.…”