Interaction Forces And Reaction Kinetics Of Ligand-Cell Receptor Systems Using Atomic Force Microscopy

<p>Atomic Force Microscopy (AFM) provides superior imaging resolution and the ability to measure forces at the nanoscale. It is an important tool for studying a wide range of bio-molecular samples from proteins, DNA to living cells. We developed AFM measurement procedures to measure protein interactions on live cells at the single molecular level. These measurements can be interpreted by using proper statistical approaches and can yield important parameters about ligand-receptor interactions on live cells. However, the standard theory for analyzing rupture force data does not fit the experimental rupture force histograms. Most of the experimental measurements of rupture force data generate a probability distribution function (pdf) with a high force tail. We show that this unexpected high force tail can be attributed to multiple attachments and heterogeneous bonding by studying a model system, biotin-avidin. We have applied our methodology to the medically relevant system of discoidin domain receptors (DDR) on live cells and their interaction with their ligand, collagen. In addition, we have also used AFM to study drug-delivery particles, in particular polymer micelles containing fluorescently labeled siRNA particles. In this study, we measured interaction forces and binding probability measurements between folate receptor functionalized cantilever and different substrates, as well as combined AFM and fluorescence microscopy.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Physics and Astronomy

Year dc:date.available

2015

Author dc:creator

• Sarkar, Anwesha

Contributors dc:contributor

• Peter M. Hoffmann

• Atomic Force Microscopy
• Collagen
• Discoidin domain receptors
• Folate receptor
• Protein-protein interactions
• Single molecule force measurements
• Biophysics
• Physics

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/1410

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-2409