Multiscale Model-Based Investigation of Functional Macromolecular Agglomerates for Biotechnological Applications

The formation of macromolecular agglomerates and ordered assemblies has diverse applications in both nature and technology. Especially biotechnology often relies heavily on (semi-)ordered macromolecular assemblies to enable specific functions. Examples are enzymatic biocatalysis enhanced through metabolic channeling as a result of structural organization of enzymes and virus-like particles (VLPs) as self-assembled transport containers for genetic materials or pharmaceuticals. In order to better understand such systems, we developed a novel multiscale method using data-driven parameterization approaches to simulate formation and properties of large macromolecular assemblies on scales of micro-meters and milli-seconds. Thus, enabling the investigation well beyond traditional methods such as molecular dynamics (MD). The method is termed the molecular discrete element method (MDEM). As model systems the calcium mediated gelation of the biopolymer alginate, self-assembly of the hepatitis B core antigen (HBcAg) into VLPs, and semi-structured agglomerate formation of the pyruvate dehydrogenase complex (PDC) were investigated at various process conditions. Experimental validation was performed using both available literature data and experimental results of collaborators showing good agreement with model predictions.