About

Luo Gu is an assistant professor of materials science and engineering at Johns Hopkins University. His laboratory studies how cells sense and respond to the mechanical and biochemical cues from their microenvironment. The findings from these studies are then used to design and create new biomaterials that provide desirable signals in a spatiotemporally controlled manner to direct cell behavior and function. His current projects focus on developing tissue-like viscoelastic biomaterials to investigate the role of matrix mechanics in stem cell biology and tissue regeneration; engineering immune niches with biomaterials for cancer immunotherapy; and creating new nanomaterials for gene editing. Gu received his bachelor’s degree in chemistry from Peking University in China in 2004, a master’s degree in chemistry from the University of California, San Diego, in 2007, and a doctorate in chemistry with a specialization in multiscale biology from UCSD in 2012. He completed his postdoctoral training at the Harvard School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering before joining the Whiting School of Engineering faculty in 2017.

Research topics

• Computer Science
• Sociology
• Computational biology
• Engineering
• Biomedical engineering
• Biology
• Materials science
• Engineering ethics
• Nanotechnology
• Data science

Selected publications

• Scenario-Based Public Values Promotion and Citizens’ Willingness to Engage in Digital Coproduction

  Public Performance & Management Review · 2025-11-01 · 2 citations

  articleSenior author
  PublisherDOI

• Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function

  Science Advances · 2025-01-01 · 24 citations

  articleOpen access

  Human mesenchymal stem cells (hMSCs) respond to mechanical stimuli, including stiffness and viscoelasticity. To date, it is unknown how extracellular fluid viscosity affects hMSC function on substrates of different stiffness and viscoelasticity. While hMSCs assume an adipogenic phenotype on gels of low stiffness and prescribed stress relaxation times, elevated fluid viscosity is sufficient to bias hMSCs toward an osteogenic phenotype. Elevated viscosity induces Arp2/3-dependent actin remodeling, enhances NHE1 activity, and promotes hMSC spreading via up-regulation of integrin-linked kinase. The resulting increase in membrane tension triggers the activation of transient receptor potential cation vanilloid 4 to facilitate calcium influx, thereby stimulating RhoA/ROCK and driving YAP-dependent RUNX2 translocation to the nucleus, leading to osteogenic differentiation. hMSCs on soft gels at elevated relative to basal viscosity favor an M2 macrophage phenotype. This study establishes fluid viscosity as a key physical cue that imprints osteogenic memory in hMSCs and promotes an immunosuppressive phenotype.

  PublisherDOI

• Cytoplasmic anillin and Ect2 promote RhoA/myosin II-dependent confined migration and invasion

  Nature Materials · 2025-06-26 · 7 citations

  articleOpen access

  Cell migration in mechanically confined environments is a crucial step of metastatic cancer progression. Nonetheless, the molecular components and processes mediating such behaviour are still not fully understood. Here we demonstrate that a pool of the scaffolding protein anillin and its cofactor Ect2, which are both predominantly nuclear proteins and critical mediators of cytokinesis, is present in the cytoplasm of multiple interphase cell types that promote confined cell migration. Confined migration in biomimetic microfluidic models triggers the actomyosin-binding-dependent recruitment of anillin to the plasma membrane at the poles of migrating cells in a manner that scales with microenvironmental stiffness and confinement. The guanine nucleotide exchange activity of Ect2 is required for its RhoA-GTPase-mediated activation of myosin II at the cell poles, enhancing invasion, bleb-based migration and extravasation. Confinement-induced nuclear envelope rupture further amplifies this process due to the release of further anillin and Ect2 into the cytoplasm. Overall, these results show how Ect2 and anillin cooperate to mediate RhoA/ROCK/myosin II-dependent mechanoadaptation and invasive cancer progression.

  PublisherOA PDFDOI

• The Effects of Matrix Mechanical Properties on Glia Behavior

  2025-01-01 · 1 citations

  book-chapterSenior author
  PublisherDOI

• Calcium sulfate microparticle size modification for improved alginate hydrogel fabrication and its application in 3D cell culture

  Frontiers of Materials Science · 2025-02-26 · 2 citations

  articleSenior authorCorresponding
  PublisherDOI

• Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis

  Communications Biology · 2025-02-23 · 3 citations

  articleOpen access1st authorCorresponding

  NOD-like receptor (NLR) family proteins are implicated in various cardiovascular diseases. However, the precise role of NLRC5, the largest member of this family, in myocardial infarction (MI) remains poorly understood. This study reveals that NLRC5 is upregulated in the hearts of both patients with MI and MI mice. Silencing NLRC5 in cardiomyocytes impairs cardiac repair and functional recovery, while its overexpression enhances these processes. Furthermore, NLRC5 promotes autophagy in cardiomyocytes, and its protective effects are diminished upon autophagy inhibition. Mechanistically, NLRC5 interacts with CAVIN1, facilitating its degradation and subsequent downregulation of CAV1, which in turn increases the expression of the ATG12-ATG5 complex to stimulate autophagy. Conversely, CAV1 overexpression partially suppresses autophagy and attenuates the improvements in cardiac function observed in NLRC5-overexpressing MI hearts. This study highlights the critical regulatory role of NLRC5 in modulating cardiomyocyte autophagy flux, suggesting that NLRC5 activation may represent a promising therapeutic strategy for MI.

  PublisherOA PDFDOI

• Viscoelastic extracellular matrix enhances epigenetic remodeling and cellular plasticity

  Nature Communications · 2025-04-30 · 36 citations

  articleOpen access

  Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function, compared to those on elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility at cis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering.

  PublisherOA PDFDOI

• Fibroblast-secreted ADAMTSL2 promotes cardiac repair after myocardial infarction by activating LRP6/β-catenin signaling

  Cellular Signalling · 2025-09-22 · 2 citations

  article
  PublisherDOI

• Disordered Glass Nanowire Substrates Produce in Vivo‐Like Astrocyte Morphology Revealed by Low‐Coherence Holotomography

  Advanced Science · 2025-11-03 · 2 citations

  articleOpen access

  Astrocytes are essential for preserving homeostasis of the central nervous system (CNS). They regulate synaptic activity and interact with the extracellular milieu via their distinctive, star-like morphology. However, there is a lack of detailed understanding of astrocyte morphology, particularly of the in vivo phenotype that is difficult to replicate in vitro and quantify using conventional imaging techniques without exogenous labels. This study marks the first demonstration of low-coherence holotomography (LC-HT), a label-free imaging technique, for 3D quantitative assessment of astrocyte morphology cultured on nanostructured substrates, which typically presents challenges for phase-based imaging. Crucially, it is shown that disordered glass nanowire (NW) substrates can induce in vivo-like astrocyte morphology in cultured rat cortical astrocytes. Compared to traditional glass substrates, astrocytes grown on disordered glass NWs substrates exhibit enhanced process branching and greater total arbor length - features typically observed in their natural, in vivo state of advanced maturation. By combining disordered glass NW substrates with LC-HT, the approach uniquely enables high-fidelity, label-free visualization of complex astrocytic morphologies, providing a powerful platform to study how nanoscale environmental cues shape astrocyte development.

  PublisherOA PDFDOI

• Figure S1 from Small Extracellular Vesicles Promote Stiffness-mediated Metastasis

  2024-05-09

  preprintOpen access

  <p>Stiffness measurements of primary patient tissues</p>

  PublisherOA PDFDOI

Frequent coauthors

• Denis Wirtz

  Johns Hopkins Medicine

  35 shared

• Joo Ho Kim

  34 shared

• Mehran Habibi

  34 shared

• Jun Du

  Chinese Academy of Sciences

  31 shared

• Alexandra Sneider

  31 shared

• T.S. Karin Eisinger‐Mathason

  31 shared

• Estibaliz Gómez‐de‐Mariscal

  Instituto Gulbenkian de Ciência

  29 shared

• Gabrielle E. Ciotti

  29 shared

Education

• Postdoctoral Fellow, School of Engineering and Applied Sciences/Wyss Institute for Biologically Inspired Engineering

  Harvard University

  2017

• Ph.D., Chemistry and Biochemistry

  University of California, San Diego

  2012

Awards & honors

• 2023 CMBE Rising Star Award