Mechanobiology and Microfluidics Lab
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Head of Laboratory
Associate Professor Sara Baratchi Baratchi
Research Overview
The Mechanobiology and Microfluidics research group focuses on pioneering artificial models of human blood vessels and heart valves using advanced microfabrication and microfluidic technologies.
Through these unique and state-of-the-art models, we systematically elucidate the molecular mechanisms that control cellular responses to hemodynamic forces, which consequently lead to the development of cardiovascular diseases.
Our research is interdisciplinary and at the interface of biology, physics, engineering, and medicine, making it suitable for students with backgrounds in both disciplines of biomedical science and biomedical engineering.
Current projects:
A Bioengineered Model of Calcific Aortic Valve Disease:
Calcific aortic valve disease (CAVD) is a common cause of mortality and morbidity in the elderly population. Due to an inadequate understanding of the mechanisms that drive the progression of aortic stenosis, there is no effective treatment for CAVD other than surgical or transcatheter valve replacement.
Although histological assessment of heart valves provides a snapshot of CAVD features, it does not reveal the complex mechanisms underlying the development of this disease. Furthermore, there are no animal models of CAVD that truly reflect human aortic disease. Our limited knowledge of the sequence of events that occur during the CAVD pathogenesis provides a major obstacle in developing medical treatments for this disease. Engineered models of valvular disease can serve a critical role in unlocking the complex pathology of CAVD, as they enable a controlled manipulation of causative connections.
This project utilises an engineered aortic valve model that mimics features found in the early and late stages of CAVD for the systematic study of CAVD pathogenesis. It utilises 3D printing and soft lithography techniques to create a CAVD model incorporating moving valves, which can be opened and closed in response to pulsatile pressure. The valves will be coated with extracellular matrix, valvular interstitial cells, and valvular endothelial cells to mimic the 3D microenvironment of the valve tissue. The model allows the stiffness, extracellular matrix thickness and composition, and stenosis level of the valves to be tuned. Using this model, we will characterise the response of valvular interstitial and endothelial cells as well as circulating immune cells and platelets to changes in hemodynamics during moderate and severe stages of CAVD in a systematic manner.
This project will provide a better understanding of the mechanisms driving CAVD progression and a platform for screening drug targets, and ultimately, the development of long sought-after medical therapy for CAVD.
A Bioengineering approach to study atrial fibrillation:
Atrial fibrillation (AF), the most prevalent sustained arrhythmia globally, is a major driver of stroke, heart failure, sudden deaths, and cardiovascular disease. Although an arrhythmia more commonly affects the elderly, AF can manifest in young and middle-aged adults as well. Thromboembolic disease, particularly stroke in the young, can lead to increased long-term morbidity, which can affect relationships, education, and employment. These outcomes not only lead to substantial healthcare costs but also pose a significant burden on public health.
Despite its widespread occurrence, our understanding of its mechanisms remains incomplete, and the available therapeutic options exhibit limited efficacy while often carrying inherent risks. Existing animal models cannot truly reflect a human cardiovascular biology as discussed above.
This project aims to develop a bioengineering model of AF to understand the fundamental biological processes that control the sensitivity of endothelial cells and blood cells to arrhythmic flows.
A Microfluidic approach to study the mechanobiology of ageing blood vessel:
Arterial stiffening in ageing adults is associated with the progression of cardiovascular diseases, hypertension, myocardial infarction and dementia. Importantly, increase in blood vessel stiffness leads to significant changes in blood flow-induced forces (both pressure and shear stress), and impacts arterial endothelium, which plays a central role in maintaining vascular integrity and homeostasis in response to hemodynamic forces.
However, it is not clear how changes in haemodynamic forces as a result of vessel stiffness affect endothelial cells biology and how the cells respond to these changes. Whether endothelial cells contribute to repair or further damage the stiffened vessel is not known, yet these cells are crucial in determining the fate of the vessel.
This project aims to study the effects of the stiffening and ECM remodelling of ageing arteries on endothelial cells. The project expects to generate new knowledge of the changes that occur in endothelial cells using a unique microfluidic technology with tunable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.
Staff
Heads: A/ Prof Sara Baratchi and A/ Prof Khashayar Khoshmanesh
Dr Ying Zhou, Post Doctoral Researcher
Chanly Chheang, Research Assistant
Austin Lai, Post Doctoral Researcher
Dr Nalin Dayawansa, PhD Student
Manijeh Khanmohammadi, PhD Student
Thayana Torquato, PhD Student
Gianmarco Concilia, PhD Student
Adam Hawke, PhD Student
Yasmin Mirzaalikhan, PhD Student
Habiba Danish, PhD Student
Panagiotis Iliopoulos, PhD Student
Sergio Aguilera Suarez, PhD Student
Collaborators
- Prof Karlheinz Peter, Baker Heart and Diabetes Institute, Australia
- Prof Elena Pirogova, School of Engineering, RMIT University, Australia
- Prof Jon Cooper, University of Glasgow, UK
- A/ Prof David W. Greening, Baker Heart and Diabetes Institute, Australia
- A/Prof Nicholas Williamson, University of Melbourne, Australia
- A/Prof Agus Salim, University of Melbourne, Australia
- A/Prof Anthony Jaworowski, Burnet Institute, Australia
- A/Prof Aaron Jex, Walter and Eliza Hall Institute of Medical Research, Australia
- A/ Prof Shi-Yang Tang, University of Southampton, UK
- Dr. Ching-Seng Ang, University of Melbourne, Australia
- Dr Charles Cox, Victor Chang Cardiac Research Institute, Australia
- Dr Kylie Quinn, School of Health and Biomedical Sciences, RMIT University, Australia
- Dr Nhiem Tran, School of Science, RMIT University, Australia
Funding
National Health and Medical Research Council (NHMRC)
Australia Research Council (ARC)
Research Outcomes
Highlighted Publications
- S. Baratchi, M. T. K. Zaldivia, M. Wallert, J. Loseff-Silver, S. Al-Aryahi, J. Zamani, P. Thurgood, N. M. Htun, D. Stu, S. J. Duffy, Antony Walton, Ha Nguyen, A. Jaworowski, K. Khoshmanesh, K. Peter, “TAVI represents an anti-inflammatory therapy via reduction of shear-stress induced, Piezo-1-mediated monocyte activation”, Circulation (2020) 142, 1092-1105
- A. Lai, A. Hawke, M. Mohammed, P. Thurgood, G. Concilia, K. Peter, K. Khoshmanesh, Sara Baratchi, “A microfluidic model to study the effects of arrhythmic flows on endothelial cells”, Lab on Chip (2024), doi.org/10.1039/D3LC00834G
- A. Lai, P. Thurgood, C. D. Cox, C. Chheang, K. Peter, A. Jaworowski, K. Khoshmanesh, S. Baratchi, “Piezo1 response to shear stress is controlled by the components of the extracellular matrix”, ACS Applied Materials & Interfaces (2022) 14, 40559–40568
- Lai, Y. C. Chen, C. D. Cox, A. Jaworowski, K. Peter, S. Baratchi, “Analyzing the shear‐induced sensitization of mechanosensitive ion channel Piezo‐1 in human aortic endothelial cells”, Journal of Cellular Physiology (2021) 236, 2976-2987
- N. Chandra Sekar, S. Aguilera Suarez, N. Nguyen, A. Lai, P. Thurgood, Y. Zhou, C. Chheang, S. Needham, E. Pirogova, K. Peter, K. Khoshmanesh, S. Baratchi, “Studying the Synergistic Effect of Substrate Stiffness and Cyclic Stretch Level on Endothelial Cells Using an Elastomeric Cell Culture Chamber”, ACS applied materials & interfaces (2023) 15, 4, 4863-4872
- P. Thurgood, S. A. Suarez, E. Pirogova, A. R. Jex, K. Peter, S. Baratchi, K. Khoshmanesh, “Tunable Harmonic Flow Patterns in Microfluidic Systems through Simple Tube Oscillation”, Small (2020) 16, 2003612
- M. Mohammed, P. Thurgood, C. Gilliam, N. Nguyen, E. Pirogova, K. Peter, K. Khoshmanesh, S. Baratchi, “Studying the effect of pulsatile flow on the mechanobiology of aortic endothelial cells using a piezoelectric pump-driven microfluidic system”, Analytical Chemistry (2019) 91, 12077-12084
- S. Baratchi, J. G. Almazi, W. Darby, F. J. Tovar-Lopez, A. Mitchell, P. McIntyre, “Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells”, Cellular & Molecular Life Sciences (2016) 73, 649-66
Research Publications
For a full list of publications, please visit https://scholar.google.com.au/citations?user=yIGfHD4AAAAJ&hl=en