Friday, May 9, 2025
5/9/2025
Understanding Impact of Controlled 3D Topographical Design on Biological Interactions - PROJECT ABSTRACT The interaction of cells with micro- and nano-scale topography is a critical signaling modality in controlling cell activity. This interaction is ubiquitous in the extracellular matrix where natural multiscale topographic structures provide mechanotransductive cues, essential for processes like cell migration and polarization. Advances in nanoengineering have led to the creation of synthetic nanoscale systems that mimic the structure and scale of the native topography, significantly enhancing our understanding of biological processes at the nanoscale. Despite these advances, there are significant gaps that impede our ability to effectively harness topographical designs and topography-cell interactions for biological research and applications. One of the key challenges is the limited understanding of how topographical cues affect the interplay between multiple biological entities at different scales. Most studies to date have primarily focused on single cell types on static topographies, overlooking the dynamic interactions between multiple biological entities in 3D space, which better mimic in vivo environments. Clinical outcomes and biological effects emerge from the collective behavior of multiple entities in 3D and cannot be captured simply by studying single cell types in 2D settings. Furthermore, current patterning techniques, such as lithography and nanogratings, are limited to small-sized 2D surfaces, hindering their progression to the (pre)clinical phase and leaving their in vivo effectiveness uncertain. Addressing these gaps, my research program is developing multidisciplinary methodologies to mimic, exploit, and quantify the complex and dynamic interacting processes between controlled topography and multiple biological entities in 3D space and time (i.e., 4D). In my lab’s first three years, we have made two major advances: (i) We developed an innovative and versatile bottom-up nanofabrication approach that enables the creation of controlled nano/micro-topographies on various substrates at large scales. This method features dynamic topography, allowing for reversible shape transformations without morphological distortion; and (ii) We studied the interactions between controlled nano/micro-topographies and a variety of single biological entities, including bacteria, tissue cells, macrophages, and exosomes. This proposal seeks to extend my lab’s capabilities, which can lead to new therapeutic and diagnostic avenues through fundamentally transformed knowledge of basic cell physiology. My goals for the next 5 years are: (1) Develop versatile 3D topographic nanopatterning tools that can accurately replicate dynamic 3D topographies found in natural biological systems; (2) Develop a suite of 3D model systems to study various types of topography-biology interactions in 3D space and across diverse pathophysiological and biomedical contexts. Importantly, the methods will be versatile, scalable, and cell/tissue/disease-agnostic, enabling enhanced fundamental understanding of material-bio interactions while laying the foundation for advances in disease diagnosis, treatment, and prevention.
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