Mechano-chemical Coupling in the Adhesion of Thin Shell Structures: Transitions between Weakly- and Well- Bonded States (CMMI ? 0900058) PI: John L. Bassani Department of Mechanical Engineering and Applied Mechanics University of Pennsylvania, PA 19104

Bonding of thin films and adhesion of biological cells are important topics with certain common mechanical, chemical, and thermodynamic characteristics that motivate the proposed research. The overall objective is to understand how the adhered state between a thin film or shell and a substrate is controlled by intrinsic physical and chemical properties. For non-conforming bodies, these states are constrained by kinematical compatibility, force equilibrium, and chemical equilibrium. Molecular information, for example, the effects of stress on the kinetics of the bond, will be incorporated into macroscopic models.

Transitions between weakly and strongly adhered states, what are referred to in the proposal as a snap-in/snap-out phenomena, have broad implications. The control of snap-in and snap-out adhesive transitions, with and without the influence of various dissipative mechanisms including the effects of diffusion and of stress on bonding, offer potential in applications ranging from micro-electro-mecahnical systems (MEMS), medical treatments, and even data storage. Snap debonding of wafers due to fabrication defects or due to moisture is a problem for MEMS technologies. Snap transitions also may be key to the attachment-detachment mechanism that are present in the natural cycles of white blood cells. Another exciting application is tissue engineering in which cells can be aligned by adhering to patterned substrates. One additional example: there have been many clinical trials for cancer treatment that attempt to breakdown the adhesion of tumor cells, and perhaps a better understanding of the mechano-chemistry of adhesion can point the way to other therapeutic advances.

Project Report

This research focused on developing an understanding adhesion of living cells with other cells and with extracellular matrix material. Mathematical models and computer simulations of the coupling between mechanical and chemical factors have been developed through NSF support for this research. Living tissue is formed largely from the adhesion of living cells. Therefore, building on the models we have developed, there is the potential to advance aspects of medical science as well as clinical treatments that can potentially benefit all of us. One prominent area of health care is the immune system, in which white blood cells (leukocytes) attach and detach to the endothelium that lines the vascular network in out body in order to perform immune-system functions. The mechanisms of attachment and detachment are not well understood, particularly as it couples to mechanical factors. One can imagine that one day health care will have a deeper scientific basis for the understanding of how cell adhesion affects our health. Time will tell. In the course of this research, we have discovered instabilities that lead to transitions between weakly and strongly adhered states which could have a significant role to play both in tissue formation as well as in the behavior of white blood cells. We also have shown that the activation of so-called cytoskeleton elements within a cell is strongly coupled to the mechanical response of what we have termed tethered shells*. This work primarily involved computer simulations of shells with tethers undergoing large deformations, which can lead to buckling instabilities, that are loaded both by chemically-active tethers and adhesive forces that act externally on the shell. The computation algorithm required to solve such a non-linear, time-dependent problem was complex and required extreme care in integration in the presence of possible instabilities. The results of this study will be available to the broader research community that spans engineering, biology, physics and chemistry. Many graduate students at Penn learned both from the outcomes of this research and from a new course on shell mechanics, which was an outgrowth from this project, that already has been taught twice so far. The key outcome from this project is a fundamental understanding of coupled mechanical and chemical mechanisms that control the response of a shell with active tethers to external stimuli including adhesive interactions and applied forces. This research is an important step in developing a rigorous model for a living cell, one that strongly couples mechanical and chemical factors. A key element of the model is accounting for both spatially and time varying fields that have been shown to be central in determining the final adhered state. As a result, we argue that the interpretation of experimental observations needs to be carried out in tandem with theoretical predictions, which because of their complexity must involve detailed numerical simulations. * A simple two-dimensional counterpart is a bicycle wheel, where the rim represents the cell membrane and the spoke the tethers. Unlike spokes though, the cytoskeleton tethers are active like muscle cells and exert contractile forces. Like spokes on a bicycle wheel, the cytoskeleton tethers greatly enhance the stiffness of an otherwise soft cell membrane.

Agency
National Science Foundation (NSF)
Institute
Division of Civil, Mechanical, and Manufacturing Innovation (CMMI)
Application #
0900058
Program Officer
Thomas Siegmund
Project Start
Project End
Budget Start
2009-09-01
Budget End
2012-12-31
Support Year
Fiscal Year
2009
Total Cost
$358,000
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104