Physical understanding of abnormal embryo development

Principal Investigator: Professor Y. Lin (Department of Mechanical Engineering)

This project is showcased as the Research Highlight (2022 April-May) in the inaugural exhibition – Engineering for Better Living in Innovation Wing Two

Project information

Introduction

Abnormal embryonic development leads to severe birth defects and diseases such as dysmelia. Recent studies have shown that the embryo of Caenorhabditis elegans, a model organism, undergoes abnormal elongation when cellular anisotropy and plasticity cannot be developed and maintained properly. However, the underlying mechanisms remain unclear.

Novelty of the Project

To understand the physical origin of abnormal embryo elongation, we developed a dynamic model (within the framework of continuum mechanics and thermodynamics) to

  1. elucidate how cellular anisotropy and plasticity are gradually developed in the embryo wall during its elongation;
  2. show how the elongation process is sustained and stabilized by the development of anisotropy and plasticity in cells;
  3. reveal that insufficient myosin activity and excessive severing of F-actin bundles are two major causes for abnormal embryo elongation.

Benefit to the Community

This study is expected to be useful for biologists, biophysicists, and biomedical engineers. Specifically,

  1. by elucidating the exact roles of intra/inter-cellular contraction, F-actin realignment and severing/re-bundling in the elongation of embryos, this work significantly advances our physical understanding of this important process;
  2. our study also indicates that abnormal embryo elongation might be rescued by restoring myosin activity and F-actin stability. This could provide new insights for the prevention and treatment of birth defects and related diseases in the future.

About the scholar

Professor Y. Lin received the BS and MS degrees in Engineering Mechanics from Tsinghua University in 1999 and 2001, respectively. He later obtained a MS degree in Applied Mathematics in 2006 and followed by a Ph.D. degree in Solid Mechanics in 2007 from Brown University. He joined the Department of Mechanical Engineering in the University of Hong Kong in 2008 after serving a brief appointment at Brown University as a post-doctoral research associate. His research interests include cellular and molecular biomechanics, and mechanics of biological materials.

Project poster
Project images
Group photos: Dr. X. Shao, Dr. Y. Lin and Dr. C. Fang (Left to Right)
Abnormal embryo development causes severe disorders and diseases.
A unified dynamic model for C.elegans embryo elongation
Cellular anisotropy and plasticity promote embryo elongation, in agreement with experiment measurements
Press release

HKU scientists research breakthrough in cell mechanics discovers abnormal embryo elongation for early treatment

The press release article can be founded in HKU Press release (https://www.hku.hk/press/news_detail_23072.html)

Fetal abnormalities are of concern to all prospective parents, and many of these problems originate from abnormalities in the development of the embryo particularly during its elongation and division.

In a recent breakthrough, a research team led by Dr. Yuan LIN, Associate Professor of the Department of Mechanical Engineering at the University of Hong Kong (HKU) has shed critical insight on what causes abnormal embryo elongation, and possible new ways of treating those disorders. The findings have been published in Science Advances.

Earlier studies with model organism Caenorhabditis elegans revealed, during its development, that the embryo of the organism undergoes a several-fold extension, driven by contractile forces generated in muscle and seam cells in the embryonic wall, without losing its structural integrity. Recent studies have shown that this elongation process is accompanied by significant cytoskeletal anisotropy and plastic deformation of cells, but how such cellular anisotropy and plasticity are developed and their role in embryo development remain unclear to scientists.

Dr. Lin and his team (including Dr. Chao Fang, Dr. Xi Wei and Dr. Xueying Shao) showed that the presence of active intercellular contraction within an embryo will trigger the alignment and severing/ re-bundling of actin filaments (Fig. 1), leading to cellular anisotropy and plasticity, elevating the internal hydrostatic pressure of embryo and eventually driving its elongation. In particular, it was found that the gradual re-alignment of actin bundles must be synchronised with the development of intracellular forces for the embryo to elongate, which is then further sustained by muscle contraction-triggered plastic deformation of cells.

The findings also suggest that pre-established anisotropy is essential for the proper onset of the elongation process while defects in the integrity or bundling kinetics of actin bundles result in abnormal embryo extension, in good agreement with experimental observations (Fig. 2).

By revealing the mechanism by which active cellular forces and physical response of cells affect the extension dynamics of embryos, the study serves as a major step in furthering our understanding of embryonic development. In addition, given that many embryo diseases are caused by defected internal structure of cells along with their abnormal mechanical behavior, the theoretical framework developed could provide critical insights for the design of new strategies in detecting and possibly treating such disorders.

Dr. Lin’s reseach team is among the world’s most active groups in cell mechanics research, particularly in elucidating the physical mechanisms behind important biological processes such as tissue morphogenesis, cell adhesion, cell migration and mechanotransduction, as well as exploring their possible biomedical applications. To achieve these goals, they have been using theoretical modeling and large-scale simulation in conjunction with experimental tools like cutting-edge micro-/nano- fabrication and characterisation techniques. Their earlier works were published in major international academic journals such as Proceedings of the National Academy of Sciences of the United States of America (PNAS) and Physical Review Letters.

Details of the published paper:
Force-mediated Cellular Anisotropy and Plasticity Dictate the Elongation Dynamics of Embryos. Chao Fang, Xi Wei, Xueying Shao and Yuan Lin.
https://doi.org/10.1126/sciadv.abg3264
Science Advances  30 Jun 2021:
Vol. 7, no. 27, eabg3264
DOI: 10.1126/sciadv.abg3264

Media enquiries: Dr. Yuan Lin, Department of Mechanical Engineering (Tel: 3917 7955; Email: ylin@hku.hk)
Ms Celia Lee, Faculty of Engineering, HKU (Tel: 3917 8519; Email: leecelia@hku.hk)
Mr Heng Cheng, Faculty of Engineering, HKU (Tel: 3917 1924; Email: hengc@hku.hk)

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