Supramolecular Self-Assembly Inside Living Mammalian Cells
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Supramolecular Self-Assembly Inside Living Mammalian Cells
Yuan Gao,1,2,3,4 Ryan Nieuwendaal,2 Boualem Hammouda,3 Cristina Berciu,5 Daniela Nicastro,5 Jack Douglas,2 Bing Xu,4 Ferenc Horkay1 1
Section on Tissue Biophysics and Biomimetics, NICHD, NIH; 2Polymers Division, NIST; 3NIST Center for Neutron Research; 4Department of Chemistry, Brandeis University 5 Department of Biology, Brandeis University;
Introduction Driven by directional interparticle interactions, e.g., hydrophobic patchy, pi-pi, dipolar, and hydrogen bonding interactions, certain small molecules self-assemble in aqueous solution to form nanofibers (or other nanostructures) and consequently result in hydrogels.1-5 Because of their inherent advantages such as biocompatibility, biodegradability, and morphological resemblance of extracellular matrix (ECM), supramolecular nanofibers/hydrogels promise applications in cell culture, drug delivery, and tissue engineering.6-13 Besides the successful incorporation of bioactive molecules in the hydrogelators which perform ECM-like materials outside biological entities,6,14,15 it is also important to evaluate the distribution of the nanofibers in the intracellular environment and to understand their interactions with cellular components. Self-assembly of biomacromolecules into fibrillar nanostructures is a fundamental and ubiquitous process in both prokaryotic and eukaryotic cells that is essential for their form and function. While the cytoskeletal filaments (e.g., F-actin, lamin, or microtubules) are essential for cell mechanics,16 the self-assembly of aberrant proteins into nanofibers is closely associated with neurodegenerative diseases, such as Alzheimer’s, Pick’s, Parkinson’s or Huntington’s disease.17 Due to their importance in cell biology, intracellular protein filaments (normal and abnormal) have attracted research interest on many levels (organismic to molecular). These studies have provided valuable insights, such as the identification of an array of cytoskeleton-regulatory proteins that are responsible for actin-based cellular phenomena,18 the elucidation of the non-covalent bonds for interconnecting the fibers in intermediate filaments,19 and the intracellular protein-degradation pathway for removing abnormal protein filaments.20 This knowledge not only contributes significantly to the understanding of molecular mechanism of intracellular protein filament formation and function, but also lays the foundation for the study of intracellular nanofibers self-assembled or polymerized from exogenous molecules, which is scientifically intriguing and potentially significant, but has barely been explored.21,22 Despite the importance of fibrillar self-assembly in cell function and disease, our understanding of the fundamental molecular factors that govern their geometry and stability remain poorly understood. For example, it is not understood why most proteins form amyloid fibers under certain conditions and it is of course important to know what conditions initiate this processes in the case of amyloid dis
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