Academic Appointments


Honors & Awards


  • "Women in Optics" - One of 15 leading female principal investigators in Optics worldwide, The International Society for Optics and Photonics - SPIE (2011)
  • "Promising young scientists" at the Nobel festivities, Science school for young scientists/Nobel committee (December 1988)

Boards, Advisory Committees, Professional Organizations


  • Chair, Applications of CARS microscopy, Photonics West, SPIE (2011 - 2014)
  • Program Committee member, Photonic Applications in Biology and Medicine, The Conference on Lasers and Electro-Optics, CLEO (2015 - 2016)
  • Chair/Coordinator, Innovative Training Network in Nonlinear Microscopy, The European Research Council (2013 - 2017)
  • Chair, The European network for CARS microscopy “microCARS” (2006 - 2011)
  • Member of the Review Board, Applied Physics, The Swedish Research Council (2004 - 2006)

Professional Education


  • PhD, Lund University, Physics (1997)
  • M.Sc., Lund University, Engineering Physics (1992)

Current Research and Scholarly Interests


“A picture is worth a thousand words”; The mission of my research is to contribute with a visual understanding for how macromolecules assemble and form functional structures in living cells/organoids/tissues and innovative biomaterials by probing inherent molecular/electronic vibrations using nonlinear laser excitation in a microscope: Coherent Anti-Stokes Raman Scattering (CARS), Stimulated Raman Scattering (SRS), Second/Third Harmonic Generation (SHG/THG), and multiphoton fluorescence emission. With these emerging microscopy techniques, no artificial labelling or sample preparation are needed, hence, macromolecular assemblies and kinetics can be visualized under natural conditions and amounts can be given in quantitative numbers at sub-micron resolution and for extended periods of time at sub-second resolution.
Beside technical development and investigations of new approaches of nonlinear microscopy, my research interest is to use them to explore disease- and age-related changes in the extracellular environment and the cellular lipid metabolism, e.g. in different cancers, liver diseases and in the aging brain. In collaboration with experts on the different topics, I investigate cells grown in 3D tissue-mimicking matrices, living organoids, and tissues donated from patients. Based on the mechanisms observed, we test new drugs, normalizing the extracellular environment and cell metabolism. By monitoring specific vibrations of the drug molecules, their distributions and cell responses can be investigated at cellular level versus time.

Stanford Advisees


All Publications


  • Tunable Control of Hydrogel Microstructure by Kinetic Competition between Self-Assembly and Crosslinking of Elastin-like Proteins ACS APPLIED MATERIALS & INTERFACES Wang, H., Paul, A., Duong Nguyen, Enejder, A., Heilshorn, S. C. 2018; 10 (26): 21808–15

    Abstract

    The fabrication of three dimensional "bead-string" microstructured hydrogels is rationally achieved by controlling the relative timing of chemical crosslinking and physical self-assembly processes of an engineered protein. To demonstrate this strategy, an elastin-like protein (ELP) amino acid sequence was selected to enable site-specific chemical crosslinking and thermoresponsive physical self-assembly. This method allows the tuning of material microstructures without altering the ELP amino acid sequence but simply through controlling the chemical crosslinking extent before the thermally induced, physical coacervation of ELP. A loosely crosslinked network enables ELP to have greater chain mobility, resulting in phase segregation into larger beads. By contrast, a network with higher crosslinking density has restricted ELP chain mobility, resulting in more localized self-assembly into smaller beads. As a proof of concept application for this facile assembly process, we demonstrate one-pot, simultaneous, dual encapsulation of hydrophilic and hydrophobic model drugs within the microstructured hydrogel and differential release rates of the two drugs from the material.

    View details for PubMedID 29869869

  • Covalently Adaptable Elastin-Like Protein-Hyaluronic Acid (ELP-HA) Hybrid Hydrogels with Secondary Thermoresponsive Crosslinking for Injectable Stem Cell Delivery ADVANCED FUNCTIONAL MATERIALS Wang, H., Zhu, D., Paul, A., Cai, L., Enejder, A., Yang, F., Heilshorn, S. C. 2017; 27 (28)
  • Maintenance of neural progenitor cell stemness in 3D hydrogels requires matrix remodelling. Nature materials Madl, C. M., LeSavage, B. L., Dewi, R. E., Dinh, C. B., Stowers, R. S., Khariton, M., Lampe, K. J., Nguyen, D., Chaudhuri, O., Enejder, A., Heilshorn, S. C. 2017; 16 (12): 1233–42

    Abstract

    Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from ∼0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodelling to facilitate cadherin-mediated cell-cell contact and promote β-catenin signalling. In two additional hydrogel systems, permitting NPC-mediated matrix remodelling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodelling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D.

    View details for PubMedID 29115291

  • Hybrid elastin-like polypeptide-polyethylene glycol (ELP-PEG) hydrogels with improved transparency and independent control of matrix mechanics and cell ligand density. Biomacromolecules Wang, H., Cai, L., Paul, A., Enejder, A., Heilshorn, S. C. 2014; 15 (9): 3421-3428

    Abstract

    Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin-like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP's lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP-polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 °C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell-matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics.

    View details for DOI 10.1021/bm500969d

    View details for PubMedID 25111283

  • Hybrid Elastin-like Polypeptide-Polyethylene Glycol (ELP-PEG) Hydrogels with Improved Transparency and Independent Control of Matrix Mechanics and Cell Ligand Density BIOMACROMOLECULES Wang, H., Cai, L., Paul, A., Enejder, A., Heilshorn, S. C. 2014; 15 (9): 3421-3428

    View details for DOI 10.1021/bm500969d

    View details for Web of Science ID 000341409800024

  • Sequence-Specific Crosslinking of Electrospun, Elastin-Like Protein Preserves Bioactivity and Native-Like Mechanics ADVANCED HEALTHCARE MATERIALS Benitez, P. L., Sweet, J. A., Fink, H., Chennazhi, K. P., Nair, S. V., Enejder, A., Heilshorn, S. C. 2013; 2 (1): 114-118

    View details for DOI 10.1002/adhm.201200115

    View details for Web of Science ID 000315121900009

    View details for PubMedID 23184558

    View details for PubMedCentralID PMC3641778