Staff member

Samuel I. Stupp

Severo Ochoa Distinguished Professor
CV Summary
Samuel Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine, and Biomedical Engineering at Northwestern University. He also directs Northwestern’s Simpson Querrey Institute for BioNanotechnology and the Center for Bio-Inspired Energy Science, an Energy Frontiers Research Center funded by the U.S. Department of Energy.

Stupp's interdisciplinary research is focused on developing self-assembling supramolecular nanostructures and materials for functions relevant to renewable energy, regenerative medicine, and robotic soft matter. He is a member of the National Academy of Sciences, the National Academy of Engineering, the American Academy of Arts and Sciences, the Royal Spanish Academy, and the National Academy of Inventors.

His awards include the Department of Energy Prize for Outstanding Achievement in Materials Chemistry, the Materials Research Society Medal Award, the International Award from The Society of Polymer Science in Japan, the Royal Society Award in Soft Matter and Biophysical Chemistry, and three national awards from the American Chemical Society: the ACS Award in Polymer Chemistry, the Ronald Breslow Award for Achievement in Biomimetic Chemistry, and the Ralph F. Hirschmann Award in Peptide Chemistry.
Staff member publications

Smith CS, Álvarez Z, Qiu R, Sasselli IR, Clemons T, Ortega JA, Vilela-Picos M, Wellman H, Kiskinis E, Stupp SI, (2023). Enhanced Neuron Growth and Electrical Activity by a Supramolecular Netrin-1 Mimetic Nanofiber Acs Nano 17, 19887-19902

Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors. We report here the development of a nanofiber-shaped supramolecular mimetic of netrin-1 with monomers that incorporate a cyclic peptide sequence as the bioactive component. The mimetic structure was found to activate the DCC receptor in primary cortical neurons using low molar ratios of the bioactive comonomer. The supramolecular nanofibers enhanced neurite outgrowth and upregulated maturation as well as pre- and postsynaptic markers over time, resulting in differences in electrical activity similar to neurons treated with the recombinant netrin-1 protein. The results suggest the possibility of using the supramolecular structure as a therapeutic to promote regenerative bioactivity in CNS injuries.

JTD Keywords: Axon growth, Netrin-1, Neuronal maturation, Neurotrophic factor mimetic, Peptide amphiphile, Synapsis

Álvarez Z, Ortega JA, Sato K, Sasselli IR, Kolberg-Edelbrock AN, Qiu R, Marshall KA, Nguyen TP, Smith CS, Quinlan KA, Papakis V, Syrgiannis Z, Sather NA, Musumeci C, Engel E, Stupp SI, Kiskinis E, (2023). Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons Cell Stem Cell 30, 219-238

Human induced pluripotent stem cell (hiPSC) technologies offer a unique resource for modeling neurological diseases. However, iPSC models are fraught with technical limitations including abnormal aggregation and inefficient maturation of differentiated neurons. These problems are in part due to the absence of synergistic cues of the native extracellular matrix (ECM). We report on the use of three artificial ECMs based on peptide amphiphile (PA) supramolecular nanofibers. All nanofibers display the laminin-derived IKVAV signal on their surface but differ in the nature of their non-bioactive domains. We find that nanofibers with greater intensity of internal supramolecular motion have enhanced bioactivity toward hiPSC-derived motor and cortical neurons. Proteomic, biochemical, and functional assays reveal that highly mobile PA scaffolds caused enhanced β1-integrin pathway activation, reduced aggregation, increased arborization, and matured electrophysiological activity of neurons. Our work highlights the importance of designing biomimetic ECMs to study the development, function, and dysfunction of human neurons.Copyright © 2022 Elsevier Inc. All rights reserved.

JTD Keywords: differentiation, force-field, laminin, migration, nanostructures, peptide amphiphiles, spinal-cord, statistical-model, supramolecular materials, Coarse-grained model, Dynamics, Extracellular matrix, Ikvav, Ipsc-derived neurons, Laminin, Neuronal maturation, Peptide amphiphiles, Supramolecular motion, Supramolecular nanofibers

da Silva, Ricardo M. P., van der Zwaag, Daan, Albertazzi, Lorenzo, Lee, Sungsoo S., Meijer, E. W., Stupp, Samuel I., (2016). Super-resolution microscopy reveals structural diversity in molecular exchange among peptide amphiphile nanofibres Nature Communications 7, 11561

The dynamic behaviour of supramolecular systems is an important dimension of their potential functions. Here, we report on the use of stochastic optical reconstruction microscopy to study the molecular exchange of peptide amphiphile nanofibres, supramolecular systems known to have important biomedical functions. Solutions of nanofibres labelled with different dyes (Cy3 and Cy5) were mixed, and the distribution of dyes inserting into initially single-colour nanofibres was quantified using correlative image analysis. Our observations are consistent with an exchange mechanism involving monomers or small clusters of molecules inserting randomly into a fibre. Different exchange rates are observed within the same fibre, suggesting that local cohesive structures exist on the basis of [beta]-sheet discontinuous domains. The results reported here show that peptide amphiphile supramolecular systems can be dynamic and that their intermolecular interactions affect exchange patterns. This information can be used to generate useful aggregate morphologies for improved biomedical function.