Force-induced single molecule/cell unbinding

Thanks to the possibility of measuring the unbinding force as a function of a loading rate, it is possible to study the dissociation of an individual molecular complex. Based on that, the energy landscape and parameters such as the position of the energy barrier, dissociation rate and lifetime of the complex can be obtained. These parameters are not accessible by other methods.

Single-molecule force spectroscopy (SMFS) showed different kinetics of single complexes formed between syndecans and the corresponding monoclonal antibodies. The dissociation of the complexes is related to the structure of the molecule. The dissociation of the syndecan-4, a molecule characterized by a lower molecular weight, is characterized by a two-barrier interaction potential. While the dissociation of syndecan-1, a molecule characterized by a larger mass, has a single barrier potential.

Force-induced unbinding can also be applied to study the properties of single molecular complexes directly on the surface of living cells. Another possibility is to quantify the adhesion forces of a single cell either to various materials or to other cells. The latter approach is called single-cell force spectroscopy. Our research is interested in quantifying the unbinding forces of both integrins and syndecans in normal and cancer cells.

References:

  1. K.Herman, A.Ptak, M.Lekka – Unbinding kinetics of syndecans by single-molecule force spectroscopy – Journal of Physical Chemistry Letters 9 (2018) 1509-1515.
  2. J.Zemla, J.Danilkiewicz, B.Orzechowska, J.Pabijan, S. Seweryn, M.Lekka ­ – “Atomic force microscopy as a tool for assessing the cellular elasticity and adhesiveness to identify cancer cells and tissues” – Seminars in Cell and Developmental Biology 3 (2018) 115-124.
  3. K. Herman, M. Weiss, M. Lekka, A. Ptak – How Complex Is the Concanavalin A–Carboxypeptidase Y Interaction? – ACS Chem. Biol., 14 (2019) 1611-1618.
  4. M. Lekka, K.Herman, J.Zemła, L.Bodek, G.Pyka-Fościak, D.Gil, J.Dulińska-Litewka, A.Ptak, P.Laidler – Probing the recognition specificity of αVβ1 integrin and syndecan-4 using force spectroscopy – Micron 137 (2020) 102888.