Aashrith Saraswathibhatla

Aashrith Saraswathibhatla

University of Wisconsin-Madison

H-index: 7

North America-United States

About Aashrith Saraswathibhatla

Aashrith Saraswathibhatla, With an exceptional h-index of 7 and a recent h-index of 7 (since 2020), a distinguished researcher at University of Wisconsin-Madison, specializes in the field of Mechanotransduction, Traction force microscopy, collective cell migration, biomechanics.

His recent articles reflect a diverse array of research interests and contributions to the field:

Cell–extracellular matrix mechanotransduction in 3D

Monocytes use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices

Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer

Nanoscale tracking combined with cell-scale microrheology reveals stepwise increases in force generated by cancer cell protrusions

Coordination of contractile tension and cell area changes in an epithelial cell monolayer

Effect of substrate stiffness on friction in collective cell migration

Coordinated tractions increase the size of a collectively moving pack in a cell monolayer

Role of Active Cell Forces in Controlling Collective Cell Migration

Aashrith Saraswathibhatla Information

University

University of Wisconsin-Madison

Position

___

Citations(all)

200

Citations(since 2020)

198

Cited By

18

hIndex(all)

7

hIndex(since 2020)

7

i10Index(all)

6

i10Index(since 2020)

6

Email

University Profile Page

University of Wisconsin-Madison

Aashrith Saraswathibhatla Skills & Research Interests

Mechanotransduction

Traction force microscopy

collective cell migration

biomechanics

Top articles of Aashrith Saraswathibhatla

Cell–extracellular matrix mechanotransduction in 3D

Authors

Aashrith Saraswathibhatla*,Dhiraj Indana*,Ovijit Chaudhuri

Published Date

2023/2/27

Mechanical properties of extracellular matrices (ECMs) regulate essential cell behaviours, including differentiation, migration and proliferation, through mechanotransduction. Studies of cell–ECM mechanotransduction have largely focused on cells cultured in 2D, on top of elastic substrates with a range of stiffnesses. However, cells often interact with ECMs in vivo in a 3D context, and cell–ECM interactions and mechanisms of mechanotransduction in 3D can differ from those in 2D. The ECM exhibits various structural features as well as complex mechanical properties. In 3D, mechanical confinement by the surrounding ECM restricts changes in cell volume and cell shape but allows cells to generate force on the matrix by extending protrusions and regulating cell volume as well as through actomyosin-based contractility. Furthermore, cell–matrix interactions are dynamic owing to matrix remodelling. Accordingly, ECM …

Monocytes use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices

Authors

Kolade Adebowale,Byunghang Ha,Aashrith Saraswathibhatla,Dhiraj Indana,Medeea Popescu,Sally Demirdjian,Jin Yang,Michael C Bassik,Christian Franck,Paul Bollyky,Ovijit Chaudhuri

Journal

bioRxiv

Published Date

2023

Circulating monocytes are recruited to the tumor microenvironment, where they can differentiate into macrophages that mediate tumor progression. To reach the tumor microenvironment, monocytes must first extravasate and migrate through the type-1 collagen rich stromal matrix. The viscoelastic stromal matrix around tumors not only stiffens relative to normal stromal matrix, but often exhibits enhanced viscous characteristics, as indicated by a higher loss tangent or faster stress relaxation rate. Here, we studied how changes in matrix stiffness and viscoelasticity, impact the three-dimensional migration of monocytes through stromal-like matrices. Interpenetrating networks of type-1 collagen and alginate, which enable independent tunability of stiffness and stress relaxation over physiologically relevant ranges, were used as confining matrices for three-dimensional culture of monocytes. Increased stiffness and faster stress relaxation independently enhanced the 3D migration of monocytes. Migrating monocytes have an ellipsoidal or rounded wedge-like morphology, reminiscent of amoeboid migration, with accumulation of actin at the trailing edge. Matrix adhesions and Rho-mediated contractility were dispensable for monocyte migration in 3D, but migration did require actin polymerization and myosin contractility. Mechanistic studies indicate that actin polymerization at the leading edge generates protrusive forces that open a path for the monocytes to migrate through in the confining viscoelastic matrices. Taken together, our findings implicate matrix stiffness and stress relaxation as key mediators of monocyte migration and reveal how monocytes use …

Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer

Authors

Julie Chang,Aashrith Saraswathibhatla,Zhaoqiang Song,Sushama Varma,Colline Sanchez,Naomi Hassan Kahtan Alyafei,Dhiraj Indana,Raleigh Slyman,Sucheta Srivastava,Katherine Liu,Michael C Bassik,M Peter Marinkovich,Louis Hodgson,Vivek Shenoy,Robert B West,Ovijit Chaudhuri

Journal

Nature Materials

Published Date

2023/11/13

Breast cancer becomes invasive when carcinoma cells invade through the basement membrane (BM)—a nanoporous layer of matrix that physically separates the primary tumour from the stroma. Single cells can invade through nanoporous three-dimensional matrices due to protease-mediated degradation or force-mediated widening of pores via invadopodial protrusions. However, how multiple cells collectively invade through the physiological BM, as they do during breast cancer progression, remains unclear. Here we developed a three-dimensional in vitro model of collective invasion of the BM during breast cancer. We show that cells utilize both proteases and forces—but not invadopodia—to breach the BM. Forces are generated from a combination of global cell volume expansion, which stretches the BM, and local contractile forces that act in the plane of the BM to breach it, allowing invasion. These results …

Nanoscale tracking combined with cell-scale microrheology reveals stepwise increases in force generated by cancer cell protrusions

Authors

Luka Sikic,Ester Schulman,Anna Kosklin,Aashrith Saraswathibhatla,Ovijit Chaudhuri,Juho Pokki

Journal

Nano letters

Published Date

2022/8/11

In early breast cancer progression, cancer cells invade through a nanoporous basement membrane (BM) as a first key step toward metastasis. This invasion is thought to be mediated by a combination of proteases, which biochemically degrade BM matrix, and physical forces, which mechanically open up holes in the matrix. To date, techniques that quantify cellular forces of BM invasion in 3D culture have been unavailable. Here, we developed cellular-force measurements for breast cancer cell invasion in 3D culture that combine multiple-particle tracking of force-induced BM-matrix displacements at the nanoscale, and magnetic microrheometry of localized matrix mechanics. We find that cancer-cell protrusions exert forces from picoNewtons up to nanoNewtons during invasion. Strikingly, the protrusions extension involves stepwise increases in force, in steps of 0.2 to 0.5 nN exerted from every 30 s to 6 min. Thus …

Coordination of contractile tension and cell area changes in an epithelial cell monolayer

Authors

Aashrith Saraswathibhatla,Jun Zhang,Jacob Notbohm

Journal

Physical Review E

Published Date

2022/2/17

During tissue development and repair, cells contract and expand in coordination with their neighbors, giving rise to tissue deformations that occur on length scales far larger than that of a single cell. The biophysical mechanisms by which the contractile forces of each cell cause deformations on multicellular length scales are not fully clear. To investigate this question, we began with the principle of force equilibrium, which dictates a balance of tensile forces between neighboring cells. Based on this principle, we hypothesized that coordinated changes in cell area result from tension transmitted across the cell layer. To test this hypothesis, spatial correlations of both contractile tension and the divergence of cell velocities were measured as readouts of coordinated contractility and collective area changes, respectively. Experiments were designed to alter the spatial correlation of contractile tension using three different …

Effect of substrate stiffness on friction in collective cell migration

Authors

Kelly Vazquez,Aashrith Saraswathibhatla,Jacob Notbohm

Journal

Scientific Reports

Published Date

2022/2/15

In collective cell migration, the motion results from forces produced by each cell and transmitted to the neighboring cells and to the substrate. Because inertia is negligible and the migration occurs over long time scales, the cell layer exhibits viscous behavior, where force and motion are connected by an apparent friction that results from the breaking and forming of adhesive bonds at the cell–cell and cell–substrate interfaces. Most theoretical models for collective migration include an apparent friction to connect force and motion, with many models making predictions that depend on the ratio of cell–cell and cell–substrate friction. However, little is known about factors that affect friction, leaving predictions of many theoretical models untested. Here, we considered how substrate stiffness and the number of adhesions affected friction at the cell–substrate interface. The experimental data were interpreted through prior …

Coordinated tractions increase the size of a collectively moving pack in a cell monolayer

Authors

Aashrith Saraswathibhatla,Silke Henkes,Emmett E Galles,Rastko Sknepnek,Jacob Notbohm

Journal

Extreme Mechanics Letters

Published Date

2021/10/1

Cells in an epithelial monolayer coordinate motion with their neighbors giving rise to collectively moving packs of sizes spanning multiple cell diameters. The physical mechanism controlling the pack size, however, remains unclear. A potential mechanism comes from assuming that cell–substrate traction forces persist over some time scale: with large enough persistence time, collective cell packs emerge. To test this hypothesis, we measured the velocity and net traction of each cell. The data showed that in addition to having some temporal persistence, tractions were spatially correlated, suggesting that cells coordinate with their neighbors to apply tractions in the same direction. Chemical inhibitors and activators of actomyosin contraction were used to determine effects of altering the traction persistence and alignment. Numerical simulations based on the self-propelled Voronoi model, augmented to include both …

Role of Active Cell Forces in Controlling Collective Cell Migration

Authors

Aashrith Saraswathibhatla

Published Date

2021

During tissue development, tissue repair, and disease spread, cells generate mechanical forces and migrate collectively, however, the precise relation between cell forces and collective motion is unclear. This thesis investigated the precise role of cell forces in controlling two different modes of collective migration in a cell monolayer—cell rearrangement, and coordinated motion of a collective cells.

Spatiotemporal force and motion in collective cell migration

Authors

Aashrith Saraswathibhatla,Emmett E Galles,Jacob Notbohm

Journal

Scientific Data

Published Date

2020/6/24

Cells move in collective groups in biological processes such as wound healing, morphogenesis, and cancer metastasis. How active cell forces produce the motion in collective cell migration is still unclear. Many theoretical models have been introduced to elucidate the relationship between the cell’s active forces and different observations about the collective motion such as collective swirls, oscillations, and rearrangements. Though many models share the common feature of balancing forces in the cell layer, the specific relationships between force and motion vary among the different models, which can lead to different conclusions. Simultaneous experimental measurements of force and motion can aid in testing assumptions and predictions of the theoretical models. Here, we provide time-lapse images of cells in 1 mm circular islands, which are used to compute cell velocities, cell-substrate tractions, and …

Tractions and stress fibers control cell shape and rearrangements in collective cell migration

Authors

Aashrith Saraswathibhatla,Jacob Notbohm

Journal

Physical Review X

Published Date

2020/1/23

Key to collective cell migration is the ability of cells to rearrange their position with respect to their neighbors. Recent theory and experiments demonstrate that cellular rearrangements are facilitated by cell shape, with cells having more elongated shapes and greater perimeters more easily sliding past their neighbors within the cell layer. Though it is thought that cell perimeter is controlled primarily by cortical tension and adhesion at each cell’s periphery, experimental testing of this hypothesis has produced conflicting results. Here we study collective migration in an epithelial monolayer by measuring forces, cell perimeters, and motion, and find all three to decrease with either increased cell density or inhibition of cell contraction. In contrast to previous understanding, the data suggest that cell shape and rearrangements are controlled not by cortical tension or adhesion at the cell periphery but rather by the stress …

See List of Professors in Aashrith Saraswathibhatla University(University of Wisconsin-Madison)

Aashrith Saraswathibhatla FAQs

What is Aashrith Saraswathibhatla's h-index at University of Wisconsin-Madison?

The h-index of Aashrith Saraswathibhatla has been 7 since 2020 and 7 in total.

What are Aashrith Saraswathibhatla's top articles?

The articles with the titles of

Cell–extracellular matrix mechanotransduction in 3D

Monocytes use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices

Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer

Nanoscale tracking combined with cell-scale microrheology reveals stepwise increases in force generated by cancer cell protrusions

Coordination of contractile tension and cell area changes in an epithelial cell monolayer

Effect of substrate stiffness on friction in collective cell migration

Coordinated tractions increase the size of a collectively moving pack in a cell monolayer

Role of Active Cell Forces in Controlling Collective Cell Migration

...

are the top articles of Aashrith Saraswathibhatla at University of Wisconsin-Madison.

What are Aashrith Saraswathibhatla's research interests?

The research interests of Aashrith Saraswathibhatla are: Mechanotransduction, Traction force microscopy, collective cell migration, biomechanics

What is Aashrith Saraswathibhatla's total number of citations?

Aashrith Saraswathibhatla has 200 citations in total.

What are the co-authors of Aashrith Saraswathibhatla?

The co-authors of Aashrith Saraswathibhatla are Wendy C. Crone, Ovijit Chaudhuri, Rastko Sknepnek, Silke Henkes, JC Ralphe, Jacob Notbohm.

    Co-Authors

    H-index: 40
    Wendy C. Crone

    Wendy C. Crone

    University of Wisconsin-Madison

    H-index: 40
    Ovijit Chaudhuri

    Ovijit Chaudhuri

    Stanford University

    H-index: 28
    Rastko Sknepnek

    Rastko Sknepnek

    University of Dundee

    H-index: 23
    Silke Henkes

    Silke Henkes

    University of Bristol

    H-index: 21
    JC Ralphe

    JC Ralphe

    University of Wisconsin-Madison

    H-index: 21
    Jacob Notbohm

    Jacob Notbohm

    University of Wisconsin-Madison

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