Fouling behavior of protein in mixed solvent systems: A combined experimental and simulation study.

Membrane fouling in organic solvent environments remains poorly explored despite its significance in chemical and pharmaceutical industries. This study uses molecular dynamics (MD) simulations and experiments to explore lysozyme fouling in water, as well as four organic solvent environments, namely, 30 % v/v and 50 % v/v isopropyl alcohol (IPA), and 30 % v/v and 50 % v/v dimethyl sulfoxide (DMSO). Experimentally, flux declines were least with IPA and worst with DMSO. Biased simulations indicate the worst fouling in DMSO is tied to the most attractive lysozyme-membrane energy in the presence of DMSO. However, the relative attractive energies for IPA and water do not agree with the relative flux declines, indicating other factors are more influential when the interaction energies are similar. To understand the gentler flux decline for IPA despite the more attractive lysozyme-membrane energy, radial distribution functions (RDFs) were obtained from unbiased simulations. Analyss of the water and solvent films around both the membrane and the lysozyme molecule reveal that the denser water film around both entities induced by the presence of IPA serves as a barrier for fouling and thus leads to less flux decline. The results underscore the complexity of fouling in organic solvent systems, cautioning against direct use of the understanding based on aqueous systems. [Display omitted] • Membrane fouling by lysozyme in water, IPA and DMSO studied. • Flux decline worst in DMSO and least in IPA. • Worst fouling in DMSO tied to most significant lysozyme-membrane attraction. • Least fouling in IPA tied to denser water film around membrane and lysozyme. • Both biased and unbiased molecular dynamics simulations needed for full explanation. [ABSTRACT FROM AUTHOR]