(334ah) A Systematic Multiscale Computational Approach for Engineering Novel Adaptive Materials for Biological Applications

My primary research interests are in the application and development of multiscale modeling frameworks for the rational design of functional and adaptive polymeric materials to address challenges related to drug screening and drug delivery. Technological innovations over the last several decades have been powered solely by our ability to uniquely understand the relationship between the chemistry of materials and their emergent macroscopic properties. In fact, these have led to the development of several novel classes of bulk materials such as thermoplastics and thermosets, which are today used widely in both pharmaceutical and manufacturing industries. Recently, to diversify the design parameter space, efforts are being focused on engineering complex materials (for ex. polymer grafted nanoparticle) that comprise two or more constituents with different chemistries. The central idea here is to leverage the intriguing behaviors arising at the interfaces formed by the constituents so that several materials with different macroscopic properties but with little variations in their chemistry can be designed. Though this approach sounds promising, each of these materials is still engineered for a specific targeted application and thus, it would be highly valuable to have one material that can be tuned systematically by suitable external perturbations such that it dynamically alters its microscopic structure and provides different functionalities.

I am particularly interested in identifying the various factors that can be used to realize such adaptive materials. Biology, especially, has umpteen number of examples where protein complexes self-assemble into different higher-order structures depending on several environmental cues such as concentrations, external forces, presence of salts, etc. For example, it is known that actin filaments inside cells form various structures like crosslinked networks, bundled filaments, branched filaments, and so on depending on their concentration and interactions with other proteins. I am interested in elucidating the molecular drivers of these delicate processes and translate them to computationally design synthetic materials with wide-ranging implications. My initial focus is on developing materials that can adaptively recapitulate cellular architectures for drug screening and targeting purposes. Such material when synthesized experimentally would enable rapid and high throughput screening of various drug candidates and identify potential drugs with increased efficiency. My approach will involve a systematic application of multiscale modeling techniques such as atomistic, coarse-graining, enhanced sampling, Monte-Carlo methods, etc. to develop computational models across varying length and time scales as required to understand these complex processes in detail.

Research Experience

My research from Ph.D. to postdoc has always focused on elucidating the fundamental molecular mechanisms connecting a material’s structure with its properties. I have worked on several classes of materials ranging from bulk and interfacial polymeric systems to biological protein complexes using multiscale modeling techniques to uncover the molecular determinants of their macroscopic transport, volumetric, thermal, and mechanical properties. In one of the projects during my Ph.D., I identified the key connections between the chemistry of various polyacrylate gels and the transport of small molecules (water and ethanol) through them. In fact, I also studied how these relationships change with the introduction of an interface by supporting polyacrylate gels on another hard substrate. In these studies, I systematically characterized the effects of physical and chemical characteristics of polymers such as their flexibility, hydrophobicity, and interfacial interactions on the transport properties of penetrant molecules. These results are highly generalizable to other polymeric systems and can aid in the design of efficient membranes for separation applications. In my postdoctoral training, I worked on developing a first-of-its-kind particle-based reactive-diffusive coarse-grained model of actin filaments to unravel the various factors driving the formation of higher-order actin assemblies inside a cell. Specifically, I demonstrated how the application of external forces can alter the actin filament structure in turn affecting the overall functionalities of the cell. Although the exact mechanisms leading to the formation of these structures are not known completely, it is established that they impart cells with diverse functionalities such as their ability to move, divide, and transport cargo. A clear understanding of the mechanisms underlying these processes would enable one to engineer adaptive materials that can dynamically alter their structure and provide various functionalities. A key aspect of all my prior works is the application of multiscale computational modeling approaches such as Monte Carlo, atomistic molecular dynamics, coarse-graining, enhanced sampling, and Markov State models to seamlessly connect information across length and timescales thereby allowing to systematically investigate the emergent macroscopic behavior from microscopic mechanisms. In summary, I have more than 7+ years of experience in applying the above computational methods to study a wide variety of systems such as synthetic crosslinked polymer networks, hydrogels, supported polymers, polymer thin films, and protein complexes. I am also highly proficient in (1) implementing new theoretical methods as computational tools using C++/MPI parallel and (2) in automating simulation protocols and data analysis procedures using a combination of C++, MATLAB, Python, and Linux.

Postdoctoral work: "Multiscale Modeling of Actin Filament Networks" under the guidance of Prof. Gregory A. Voth at the University of Chicago.

Ph.D. Dissertation: "Structural and Dynamic Properties of Penetrant Molecules in Unsupported and Supported Hydrated Gels" under the guidance of Prof. Rajesh Khare at Texas Tech University