| Autor: |
Imre Derényi, Mingzhai Sun, Phillip Stein, Gabor Forgacs, Marius C. Staiculescu |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Biophysical Journal. 98:285a |
| ISSN: |
0006-3495 |
| DOI: |
10.1016/j.bpj.2009.12.1556 |
| Popis: |
Hyaluronan (HA), an unbranched non-sulfated glycosaminoglycan, is an important component of the extracellular and pericellular matrix of various cell types. It has key roles in many biological processes such as wound healing, angiogenesis, embryonic development, tumor progression and invasion. HA is especially abundant around tumor cells in malignant gliomas where it is associated with high invasivity and a poor prognosis. However it is unknown how malignancy is correlated with the biomechanical properties of the cellular glycocalyx and the lifetime of the chemical bonds formed by HA with its ligands. Here we introduce a method applicable to the study of biophysical properties of cellular glycocalyx through tether extraction. Specifically, we reveal the extent of the cellular ECM of a glioma cell line (HB), we demonstrate that tethers formed through non specific binding can be pulled from the cellular glycocalyx and by using a magnetic tweezers we determine the lifetime of these tethers. To calculate lifetime we simultaneously extract multiple tethers under constant force using paramagnetic beads as force transducer. We demonstrate that the stochastic lifetimes of these tethers and thus the bonds they are associated with are exponentially distributed and can be parametrized by a generalized Bell model. We determine the maximum likelihood estimates of the relevant parameters, such as force-free dissociation constant and reactive compliance. We test the consistency of our approach using computer simulations. This method could be employed in the development of therapies which interfere with HA organization and HA-receptor binding. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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