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Innovative Tools for Three Dimensional Traction Force Microscopy of Single Cells

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA224898-01
Agency Tracking Number: R41CA224898
Amount: $149,448.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA17-148
Timeline
Solicitation Year: 2017
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-21
Award End Date (Contract End Date): 2019-03-20
Small Business Information
10 EXECUTIVE PARK DR
Clifton Park, NY 12065-8649
United States
DUNS: 012076795
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 OTTMAR KLAAS
 (518) 892-4768
 oklaas@simmetrix.com
Business Contact
 MARK BEALL
Phone: (518) 348-1639
Email: mbeall@simmetrix.com
Research Institution
 RENSSELAER POLYTECHNIC INSTITUTE
 
110 Eighth Street
Troy, NY 12180-3590
United States

 Nonprofit College or University
Abstract

Project Summary
Tractions exerted by individual cells on their surroundings play a critical role in mechanical events in biology
such as tissue contraction folding cell shape changes or cell movements and in many basic cellular
functions such as biochemical signaling proliferation and differentiation These processes are in turn
implicated in the progression of diseases like cancer atherosclerosis and other chronic fibrotic conditions
Recently this remarkable link has been utilized to develop exciting new therapeutic interventions that rely on
disrupting mechano signaling machinery within the cell and the pathways that lead to the remodeling of the
extra cellular matrix ECM
Techniques that can precisely quantify the spatial variation and heterogeneity of cellular traction within and
between cells have found important applications in understanding and controlling these processes Of these
three dimensional traction force microscopy D TFM has emerged as a particularly valuable tool since it is
applied to cells embedded in a three dimensional ECM the natural state for most cells Current D TFM
approaches are challenged by the critical steps of using optical images to generate a D geometrical model of
the matrix surrounding the cell and inferring cellular tractions from displacement estimates of micro beads
embedded in the matrix Approximations incurred in these steps lead to significant errors in computed tractions
that in turn lead to erroneous biological conclusions Thus there is critical need to develop more accurate and
high resolution D TFM techniques
The long term objective of the proposed research is to improve and automate the D TFM process so that it
can be effectively used to answer mechanobiological questions and design new therapeutic interventions This
will be accomplished by a applying advanced segmentation and mesh generation techniques to optical
images to generate D geometric models and finite element meshes of the matrix surrounding a cell and b
by developing and implementing new algorithms to determine the spatial distribution of cellular tractions from
measured micro beads displacements while accounting the nonlinear elastic response of the matrix These
developments will be validated through benchmark studies and their utility will be demonstrated by quantifying
the traction exerted by cancer cells embedded in a synthetic extracellular matrix
Project Narrative
Tractions exerted by individual cells on their surroundings play a critical role in mechanical events in biology
such as tissue contraction and folding and in many basic cellular functions such as biochemical signaling
proliferation and differentiation which are implicated in the progression of diseases like cancer
atherosclerosis and other chronic fibrotic conditions Recently this remarkable link has been utilized to
develop exciting new therapeutic interventions that rely on disrupting mechano signaling machinery within the
cell and the pathways that lead to the remodeling of the extra cellular matrix ECM The long term objective of
the proposed research is to improve and automate techniques to quantify cellular tractions that can be used to
better understand the role of tractions in biomechanical signaling and in the design new therapeutic
interventions that target these pathways

* Information listed above is at the time of submission. *

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