Understanding, manipulating and controlling cellular adhesion processes is crucial to developing strategies among others, to target drug delivery via the circulatory system, grow self-assembling tissue structures in bioreactors, and miniaturize biosensors for the detection of environmental bacteria. Yet, key issues in our knowledge of cell-cell adhesion under hydrodynamic shear flow conditions remain unresolved. Therefore a computational model based on the immersed boundary method is being developed by the applicants to simulate cell-cell interactions that accounts for both the molecular interactions and the response of the cell membrane to the bulk flow. The proposed construction and development of the numerical tools will be guided and validated by measurements of receptor-mediated leukocyte-Staphylococcus Aureus bacterial cell interactions under shear conditions, critical to the immune response. Staphylococcus Aureus bacterial strains are responsible for infections which may lead to devastating consequences including sepsis with multi-organ failure, endocarditis, arthritis, vertebral osteomyelitis, epidural abscess and endophthalmitis. Our computational model of a cell in a shear flow is used to simulate intercellular collisions between deformable cells. Moreover, by integrating the deformable cell model with a probablistic model of receptor-ligand binding, important biomechanical and kinetic parameters for leukocyte-S. Aureus adhesive interactions can be calculated. Incorporating realistic cellular details will enable us to better estimate the model parameters such as intercellular contact area, contact duration and compressive and tensile forces as a function of the cellular properties and hydrodynamic shear that influence cellular adhesion. The proposed studies will also provide a framework for analyzing other receptor-mediated cellular interactions that play a fundamental role n diverse processes in biotechnology and cell physiology, and will significantly advance our understanding at the interface of fluid physics, vascular biology and nano-scale molecular interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI063366-03
Application #
7216394
Study Section
Special Emphasis Panel (ZRG1-MABS (01))
Program Officer
Peters, Kent
Project Start
2005-02-15
Project End
2010-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$303,183
Indirect Cost
Name
University of Maryland Balt CO Campus
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
061364808
City
Baltimore
State
MD
Country
United States
Zip Code
21250
Gupta, V K (2017) Effect of cyto/chemokine degradation in effective intercellular communication distances. Physica A 468:244-251
Gupta, V K (2015) Effects of cellular viscoelasticity in multiple-bond force spectroscopy. Biomech Model Mechanobiol 14:615-32
Gupta, V K (2015) Effects of cellular viscoelasticity in lifetime extraction of single receptor-ligand bonds. Phys Rev E Stat Nonlin Soft Matter Phys 91:062701
Gupta, V K (2014) Stochastic simulation of single-molecule pulling experiments. Eur Phys J E Soft Matter 37:99
Gupta, V K (2013) Rupture of single receptor-ligand bonds: a new insight into probability distribution function. Colloids Surf B Biointerfaces 101:501-9
Gupta, V K (2013) Rupture of multiple catch-slip bonds: Two-state two-pathway catch-slip bonds. Eur Phys J E Soft Matter 36:133
Szatmary, Alex C; Eggleton, Charles D (2012) Elastic capsule deformation in general irrotational linear flows. Fluid Dyn Res 44:55503
Gupta, V K; Neeves, K B; Eggleton, C D (2012) Effect of viscoelasticity on the analysis of single-molecule force spectroscopy on live cells. Biophys J 103:137-45
Gupta, V K (2012) Effect of viscous drag on multiple receptor-ligand bonds rupture force. Colloids Surf B Biointerfaces 100:229-39
Gupta, V K; Eggleton, C D (2012) A theoretical method to determine unstressed off-rate from multiple bond force spectroscopy. Colloids Surf B Biointerfaces 95:50-6

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