Tissue of Lives

Discovering the role of viscosity in regulating the behaviour of living cells is major breakthrough for tissue engineering and could lead to better cultivation of human tissue and organs.

Scientists have long researched ways to direct cell behaviour and functioning in the hope of furthering their understanding of how to cultivate and regenerate human tissue. Now Dr Lin Yuan, from the Department of Mechanical Engineering, working alongside an international team, has revealed for the

first time how material viscosity influences the different behaviours of cells. This marks a significant breakthrough in the profound understanding of how cells operate in vivo.

“There has been significant work in this area for the past two decades,” said Dr Lin, who was among the first scientists to investigate cell adhesion from a mechanics viewpoint during his PhD study some 15 years ago. “It falls at the interface of cell biology, engineering and physics, so is very interdisciplinary.”

The new discovery could significantly advance regenerative medicine, or tissue engineering, which uses living cells to cultivate living tissue such as skin, blood, joints and major organs including hearts, which can then be used for transplant or repair.

Dr Lin, along with his student Dr Gong Ze, collaborated with researchers from the Universities of Pennsylvania, Virginia and Stanford, and showed how the surrounding viscosity of cells affects their response acrossa wide range of material parameters.

Their findings have been published in the noted academic journal Proceedings of the National Academy of Sciences of the United States of America.

Dr Lin said: “A vital factor in the successful cultivation of living cells is providing a proper and effective extracellular matrix [ECM] which mirrors the natural environment of the body as closely as possible. Almost all synthesised or natural ECMs have substantial viscosity – in addition to elasticity – but until now we did not know exactly what role material viscosity played in regulating cell behaviour.”

Dual approach

Dr Lin’s team utilised a combination of experimental and theoretical approaches. “We used both a stochastic model, describing the dynamics of motor clutches formed between the cell and outside in a probabilistic sense, and actual experiments, and we revealed how the viscous response of the micro-environment regulates the adhesion and spreading of cells, as well as the physical mechanisms behind.”

Specifically, their findings show that for substrates that are stiff, viscosity does not influence cell spreading since the bound clutches are saturated by the elevated stiffness. However, viscosity does stiffen soft substrates on a timescale faster than the clutch off-rate, and this enhances cell-ECM adhesion and cell spreading. “In short,” said Dr Lin, “on soft ECMs, maximum cell spreading is achieved at an optimal level of viscosity.”

The research team’s goals now concentrate on how to use their knowledge to design and make biomaterials to achieve desirable cell responses in different applications. They are already working with professors in the Li Ka Shing Faculty of Medicine on possible applications for Biliary Atresia, a liver disease which occurs in infants.

Abnormal tissue

“With this disease, the live tissue becomes increasingly abnormal,” said Dr Lin. “We seek initially to delineate the correlation between the progression of the disease and changes in the physical characteristics of the tissues, as well as related cellular activities. Hopefully, this can provide clues for the development of better treatment strategies in the future.”

Asked about the ongoing collaboration with the University of Pennsylvania on this work, Dr Lin underlined the importance of such cooperation. “ We have been working with Pennsylvania extensively for the last four or five years,” he said. “We also sent postgraduate students on extensive exchange programmes with the University, and this is absolutely key for this work – scholars need to spend time learning before they can produce good work.

A schematic illustrating the effects of material viscoelasticity on cellular behaviour based on the comparison of the clutch binding timescale, substrate relaxation timescale and adhesion lifetime scale.

Cell spreading speed is significantly influenced by the elastic and viscous parameters of the material.