Recent results:

Nano-surgery

Challenge: to use the AFM as an ultimately sharp knife to make “surgery” on a single bacterium. Lactobacillus helveticus bacteria was chemically pretreated with LiCl. It removed surface S-layer but left the bacteria alive. Then the AFM scanning was used to mechanically remove, peel off a part of the membrane. We discovered a structure of presumably Peptidoglycan strands, which had not been observed before.

Publication: Firtel, M., G. Henderson, and I. Sokolov, Nanosurgery: observation of peptidoglycan strands in Lactobacillus helveticus cell walls. Ultramicroscopy, 2004. 101(2-4): p. 105-109.

Nanoscale study of biomechanics of ageing human epithelial cells

The decrease in elasticity of epithelial tissues with ageing contributes to many human diseases. This change was previously attributed to increased crosslinking of extracellular matrix proteins. In this research, we show that individual human epithelial cells also become significantly more rigid during ageing in-vitro. Using atomic force microscopy (AFM), we found that the Young’s modulus of viable cells was consistently increased 2- to 20-fold in older versus younger cells. Our results identify a unique mechanism that might contribute to the age-related loss of elasticity in epithelial tissues.

Publications: T K. Berdyyeva, C.D. Woodworth, I. Sokolov, “Human Epithelial Cells Increase Their Rigidity with Ageing In-Vitro: Direct Measurements”. Physics in Medicine and Biology, v. 50, pp. 81-92, 2005

T K. Berdyyeva, C.D. Woodworth, I. Sokolov, “Visualization of Cytoskeletal Elements by the Atomic Force Microscope”. Ultramicrocopy, v.102,  pp. 89-198, 2005.

Public Impact: This research was highlighted on the front page of the American Physical Society News magazine (the monthly news journal of the APS) in May 2004, was overviewed in New Scientist ( March 2005, Magazine issue 2492). These results were also overviewed by BBC Healthnews, Allure magazine, Cosmetics & Toiletries Magazine, Boa Forma Magazine, Saberviver, Les Nouvelles Estètiques, Veja magazine (biggest magazine in Latin America), Skin & Aging, Advance News, etc. as well as a several newspapers in the USA, UK, Canada, France, Germany, Brazil, India, Portugal, and South Africa, etc.

Recover of elasticity of aged human epithelial cells in-vitro

In the previous accomplishment it was also found that the cells had three distinctive regions of different rigidity. In this work we found that the fibres that are responsible for the rigidity increase are mostly microfilaments, F-actin. Furthermore, using some cytotoxic drugs that inhibit polymerization of F-actin, we managed to restore the cell rigidities of old cells back to the young level in all three areas of rigidity simultaneously. These results may contribute to a treatment of the age-related loss of elasticity in epithelial tissues.

Publication: Submitted to Nanomedicine: Nanotechnology, Biology and Medicine (Nanomedicine) Igor Sokolov, Swaminathan Iyer, Craig D. Woodworth “Recover of Elasticity of Aged Human Epithelial Cells In-Vitro”.
 

Potential applications and technology transfer: The mechanism of the treatment has been filled for patent protection (I. Sokolov and C.D. Woodworth “Novel use of cytotoxic drugs for treatment and prophylaxis of aging diseases by reversing the loss of elasticity of epithelial cells due to aging”, patent pending US 60/579,165). A new spin-off company, NanoBioScientic, Inc. has been established to commercialize a newly developed skin cream for topical applications, and support clinical trials on humans. Currently, trials of this new treatment are underway on laboratory mice in collaboration with Prof. Erlichman at the animal facility at St. Lawrence University (Canton, NY).

First direct proof of change in rigidity in the activated form of the glucose/ galactose receptor from E.coli: a phenomenon that will be key to the development of biosensors

Recently a periplasmic glucose/galactose binding protein, GGRQ26C, immobilized on gold surface has been used as an active part of a glucose biosensor based on quartz microbalance technique (QCM). However the nature of the glucose detection was not clear. In this research we have found that the receptor protein film immobilized on the gold surface increases its rigidity when glucose is added, which explains the unexpected detection signal.

Publication: Igor Sokolov, Venkatesh Subba-Rao, and Linda A. Luck, “Change in Rigidity in the Activated Form of the Glucose/ Galactose Receptor from E-coli: A Phenomenon That Will Be Key to the Development of Biosensors”, Biophysical Journal, in press.

Potential applications: Since there are a host of receptors that undergo structural change when activated by ligand, the developed method can play a key role in the development and/or optimization of biosensors based on rigidity changes in biomolecules.