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Research in the laboratory is at many different hierarchical scales from single cell to monolayers, tissues and at the organ level. Students with strong backgrounds in mechanics and biology are encouraged to apply. At the cellular level, we study cell-substrate interactions using custom-built devices that can be used to exert Couette flows using a modified cone-plate rheometer placed on a microscope stage, non-equibiaxial stretch on an inverted microscope, and bidirectional oscillatory shear flows using an endothelium-on-chip microfluidic device.
Research in the laboratory is at many different hierarchical scales from single cell to monolayers, tissues and at the organ level. Students with strong backgrounds in mechanics and biology are encouraged to apply. At the cellular level, we study cell-substrate interactions using custom-built devices that can be used to exert Couette flows using a modified cone-plate rheometer placed on a microscope stage, non-equibiaxial stretch on an inverted microscope, and bidirectional oscillatory shear flows using an endothelium-on-chip microfluidic device.
Cell Mechanobiology
Cell Mechanobiology
a. Single Cell Mechanobiology
Individual cells constantly sense, generate, and respond to mechanical forces, which play a crucial role in regulating their shape, movement, and function. In our group, we study how these forces influence single-cell behavior using techniques like traction force microscopy to measure cellular forces, micropatterning to control cell shape and organization, and de-adhesion assays to examine adhesion dynamics. By integrating these approaches, we aim to uncover the fundamental mechanical principles that govern cell mechanics, migration, and adaptation to their microenvironment. Understanding these processes provides insights into tissue engineering, wound healing, and cancer metastasis.
b. Collective Cell Dynamics
Cells in our body live and work together collectively, coordinating their functions to drive essential physiological processes like embryonic development, organ formation, and wound healing. These processes rely on hundreds of cells acting as a unified entity, guided by mechanical forces across molecular, cellular, and multicellular scales. Our group investigates how these forces shape the collective behavior of epithelial cells, particularly in response to mechanical cues such as cyclic stretch. By uncovering the underlying mechanical principles and molecular mechanisms, we aim to understand how cells regulate movement and maintain tissue architecture.
Hydrogel Mechanics
Hydrogel Mechanics
Our work focuses on enhancing the mechanical properties of hydrogels, particularly their fracture toughness and failure resistance, for biomedical applications. We investigate crosslinking strategies, comparing traditional glutaraldehyde methods with methylglyoxal (MGO) treatment, which significantly improves elasticity and toughness. Using techniques like cavitation rheology and pure shear notch tests, we analyze failure mechanisms, crack propagation, and tip mechanics through high-speed imaging and digital image correlation. Our research reveals that MGO-treated hydrogels exhibit higher fracture toughness, frequent crack arrests, and tip blunting before failure. By linking hydrogel microstructure to mechanical behavior, we aim to develop tougher, more resilient hydrogels for tissue engineering and soft robotics.
Organ-on-chip
Organ-on-chip
Atherosclerotic plaque formation primarily occurs on arterial bifurcations, curved sections of arteries, and regions of flow stagnation. This is because changes in the wall shear stress magnitude and direction experienced by endothelial cells on the arterial wall can alter the balance of pro- and anti-atherosclerotic signals and facilitate the release of inflammatory markers.
Current microfluidic channels that attempt to recreate the arterial mechanical environment fail to create controlled, multidirectional variations of the wall shear stress on endothelial cells cultured on its surface. We have developed a novel organ-on-chip platform "Endothelium-on-Chip" that creates controlled, multi-directional temporal variations in the wall shear stress on endothelial cells cultured on the device centroid.
We use this device to investigate the effects of bidirectional shear stress on endothelial cell morphology, proliferation, nuclear disruption, etc.
We are currently modifying this device to measure permeability of the endothelial monolayer at different amounts of bidirectional shear stress. Additionally, we are combining multiple channels using a total of only two inlets and a reservoir to look for multiple markers in a single experiment. Future directions involve integrating bidirectional stretch and inflation into the microfluidic channel.
Tissue Biomechanics
Tissue Biomechanics
Arteries continually undergo cyclic expansion and contraction to fulfil varying hemodynamic demands. Fibrotic arterial diseases are associated with elastic fiber degradation, collagen deposition, and their subsequent cross-linking, which results in higher tissue stiffness and extracellular matrix remodelling. Thoracic aortic aneurysms (TAA), and those leading to dissections (TAD), are associated with a significant risk of mortality, morbidity, and emergency surgeries. We worked with clinicians in Narayana Hrudayalaya, Bangalore and tested arterial tissues from patients undergoing replacement surgery. See our work in J. Biomech. Engg. that adds emphasis to growth and remodeling in arteries. In collaboration with Prof. Jaywant Arakeri (ME, IISc), we investigated the differences in flows through highly curved tubes with curvatures similar to the aorta. This work, published in J. Fluid Mechanics, was completed by two jointly supervised M.Tech. students, Mr. Ashlin Augusty and Mr. Vamsi Krishna. We showed radially inward moving secondary flows that have the structure of wall jets on the straight walls; their subsequent collision on the inner wall leads to a radially outward moving jet. We demonstrated that the flow separation on the inner wall, reported in several previous studies, has origins in the secondary flows and not the axial pressure gradient proposed earlier. We also used patient specific geometries of the ascending aorta (AA) and the internal carotid artery (ICA), with and without aneurysms, and quantified the flow physics in these vastly different geometries using computational fluid dynamics. Our work (J. Biomechanics, 2020) shows comparisons in various flow metrics, such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and transWSS, at these locations. We propose a novel graphical representation of WSS using shear rosettes to map temporal changes in the flow dynamics during a cardiac cycle at any spatial location on the vessel surface. We also define a new metric, anisotropy ratio, using the shear rosette which is useful to describe the uni-directional and bi-directional effects of flows.
Bioinspired Materials
Bioinspired Materials
Mechanical behavior of living matter is governed not only by the short-term elastic or viscoelastic response to loading, but also by growth and remodeling at longer time scales which plays an important role in tissue properties and adaption. Natural biomaterials and mechanisms are of much interest to the lab. We study cutting by insects during oviposition to lay eggs, or by mandibles to cut substrates. We are also interested in fiber reinforcement in tissues, such as myocardium and arteries, that we study in the lab. Check some of the papers from this work for more details.
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