Mechanobiological regulations of collective cell movement: insights from in vivo to in vitro

Collective cell moment is a complex phenomenon in which cells integrate global and local cues to determine their collective positional changes. This process is fundamental to various tissue morphogenesis during embryonic development, and also plays roles in immune responses and diseases such as cancer. While significant progress has been made in identifying molecular and chemical regulators, the importance of mechanical cues has only been emerging in the last decades, primarily through in vitro and/or in single-cell studies. Our understanding of mechanical regulations in vivo, particularly in collective cell movement, is still limited. This knowledge gap aligns with the challenges in tissue engineering, where synthetic tissues for disease modeling and drug screening struggle to replicate the structural complexity of their native counterparts. As Richard Feynman famously stated, “What I cannot create, I do not understand.” The Weng lab aims to bridge in vivo and in vitro studies by integrating biology and engineering. The overall vision is to decode and harness the fundamental mechanical principles from collective cell behaviors during tissue morphogenesis, and to advance technical innovation in creating functional 3D tissues and organs. Two synergistic strategies will be employed to achieve this goal: (1) Understanding mechanical regulations of collective cell movement in vivo, and (2) engineering synthetic cues to control these regulations and recreate collective cell movement by design in vitro. Research in the Weng lab currently focuses on convergent extension (CE), a conserved collective cell movement critical for the elongation of body axis and multiple tissues during development. Using Xenopus laevis embryos and Xenopus and mammalian cells as the in vivo and in vitro models, complemented by in silico computational models, the lab studies multiscale mechanical regulation of CE. Over the next five years, this research program aims to address two key questions: (1) How do mechano-sensing and -responses between individual cells instruct CE in vivo? (2) Is it possible to engineer mechanical conditions that replicate in vivo environments to leverage cells’ mechano-sensing and -responses, eliciting CE-like collective cell movement in vitro? These studies will advance our understanding of mechanical regulations in CE, and identify key principles that warrant further exploration into other forms of collective cell movement. Additionally, this research will uncover new targets as the Weng lab continues to decode and engineer the mechanical feedback mechanisms regulating collective cell behaviors. In the long term, this program will also contribute to the fundamentals of mechanobiology and tissue engineering, as well as the prevention and treatment of aberrant collective ell movement in congenital diseases and cancer metastasis. Project Number: 1R35GM162386-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Shinuo Weng | Institution: JOHNS HOPKINS UNIVERSITY, BALTIMORE, MD | Award Amount: $412,124 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award - D Study Section[MRAD] View on NIH RePORTER: https://reporter.nih.gov/project-details/11272059