Ramsey A Foty, PhD CAB 7070 732-235-7482 fotyra@umdnj.edu

The physical forces underlying cell-cell cohesion and cell-substratum adhesion and their molecular determinants, are powerful mediators of embryonic development, cancer progression, and tissue-biomaterial interaction. Our laboratory employs a novel in vitro method, tissue surface tensiometry (TST), to simultaneously measure various biophysical properties of tissues including elasticity (a measure of a tissue’s ability to deform in response to an applied stress), viscosity (an indication of cellular motility within a tissue), and cohesivity (a dynamic and complex manifestation of the binding energy between cells).  Our laboratory has four major areas of interest all focusing on the application of this technology to explore fundamental issues regarding cell-cell and cell-substratum interaction in morphogenesis, cancer progression and tissue engineering.  Ongoing projects in the lab include (1) application of TST to study the biophysical, cellular and molecular changes accompanying the transition of prostate cancer from androgen dependence to androgen independence; (2) development of a novel in vitro liquid miscibility assay to explore endothelial cell-tumor cell interaction in bone-specific metastasis of prostate cancer; (3) assessment of whether tumor physical properties are predictive of aggressiveness in brain cancer; (4) exploring the molecular and biophysical basis of self-assembly in pancreatic islets. We have also established a collaboration with the laboratory of Dr. Siobhan Corbett to study the contribution of integrin-fibronectin interaction in mediating strong cell-cell cohesion of three-dimensional cellular aggregates in normal and malignant tissues.

Studies from our laboratory have demonstrated that tissue physical properties 1) can be used to predict and control the spatial relationship between different embryonic tissues^1,2 and also between genetically engineered cells^3,4, (2) can strongly influence the ability of tissues to interact with biomaterials⁵, (3) arise directly as a consequence of cell-cell⁶ and cell-substratum adhesion⁴, (4) correlates with invasive potential of lung tumors⁷, fibrosarcomas⁸, brain tumors⁹, and (5) can be altered not only through direct manipulation of cadherin-based intercellular cohesion^3,5,7 but also by manipulation of key ECM molecules such as FN^4,10. For comprehensive reviews see^11,12.

Comment 1    Comment 2

Two N-cad-transfected L cell clones (LN4 and LN2a), expressing N-cad at their surfaces in the ratio of 2.4 : 1, were stained with the fluorescent membrane intercalating dyes PKH2 and PKH26, (Sigma-Aldrich), mixed in equal proportions and cultured as hanging drops. (A) Confocal optical section through an aggregate after 4 h of incubation, showing initial cell mixture. (B) Confocal optical section through another aggregate after 24 hours of incubation. As predicted by the DAH, the LN2a cell line, expressing the lower level of N-cad (σ ~ 2.4 erg/cm2), here labeled red, envelops the LN4 cell line expressing higher amounts of N-cad (σ ~ 5.6 erg/cm2), here labeled green.

Literature Cited

1. Foty RA, Forgacs G, Pfleger CM, Steinberg MS. Liquid properties of embryonic tissues: Measurement of interfacial tensions. Physical Review Letters 1994;72(14):2298-301.
2. Foty RA, Pfleger CM, Forgacs G, Steinberg MS. Surface tensions of embryonic tissues predict their mutual envelopment behavior. Development 1996;122(5):1611-20.
3. Duguay D, Foty RA, Steinberg MS. Cadherin mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev Biol 2003:In press.
4. Robinson EE, Zazzali KM, Corbett SA, Foty RA. a5b1 integrin mediates strong tissue cohesion. J Cell Sci 2003;116(Pt 2):377-86.
5. Ryan MJ, Jeffries P, Bridge PD, Smith D. Developing cryopreservation protocols to secure fungal gene function. Cryo Letters 2001;22(2):115-24
6. Foty RA, Steinberg MS. The differential adhesion hypothesis: a direct evaluation. Dev Biol 2004:(in press).
7. Foty RA, Steinberg MS. Measurement of tumor cell cohesion and suppression of invasion by E- or P-cadherin. Cancer Res 1997;57(22):5033-6.
8. Foty RA, Corbett SA, Schwarzbauer JE, Steinberg MS. Dexamethasone up-regulates cadherin expression and cohesion of HT-1080 human fibrosarcoma cells. Cancer Res 1998;58(16):3586-9.
9. Winters BS, S. S, Foty RA. Biophysical measurement of brain tumor cohesion. Int J Cancer 2004;(in press).
10. Robinson EE, Foty RA, Corbett SA. Fibronectin matrix assembly regulates a5b1-mediated cell cohesion. Mol Biol Cell 2004;12:12.
11. Foty RA, Steinberg MS. Cadherin-mediated cell-cell adhesion and tissue segregation in relation to malignancy. Int J Dev Biol 2004;48(5-6):397-409.
12. Foty RA. From bugs to slugs: molecular and biophysical determinants of cell sorting. Anatomical Record 2005:(in press).