The Macromolecular, Supramolecular and Nanochemistry (MSN) Program at the National Science Foundation supports the research of Professor Alexander Li and his group at Washington State University to develop new molecular tools for measuring forces between molecules. This research investigates the use of folded, yet stretchable oligomers/polymers as force sensors for revealing molecular forces that play important roles in biological systems.
The development of a molecular force sensor that can sense force applied over a defined distance (in nanometer scale) would provide a useful tool for studying chemical and biological systems and would advance our knowledge of structure and dynamics of self-assembled systems. This project provides interdisciplinary research training to students. Science workshops will be offered to arouse the interest of middle and high school students (including students from socio-economically disadvantaged families) in science.
Life is powered by chemistry through a web of molecular interactions including cargo transportation invoked by mechanical force activation. These forces or movements generated by biomolecules are fundamental to life and it is important to understand the underpinning principles that govern how they operate. Thus the goal of this project has been to design, make, and apply polymeric probe to gauge the associated molecular forces that play the significant roles in natural systems. The results would be a new class of molecular tools, capable of gauging molecular forces at pico Newton levels and measuring distance at the nanometer scale. Because the resulting molecular tools are essentially on the scale of macromolecules, they can operate in area that traditional instruments cannot operate effectively. For example, molecular tools can function in side the body or inside a living cell, but typical medical equipment cannot carry out such measurements. The processes of life are generally performed through many concerted mechanisms involving generation of molecular forces at the nanometer-sized molecular assemblies. However, current ability to probes such processes are rather limited because traditional tools are not designed for these purposes. Therefore, developing molecular tools is significant because it addresses a critical need in capability and an unfilled gap in knowledge. The principal investigator of this project has been studying foldable polymers and fluorescent molecular probes. In this project, he has created new molecular building blocks for foldable polymers and assembled these building blocks into highly fluorescent polymers as molecular probes. These foldable and fluorescent polymers are not proteins or DNA, and thus they are not subjective to enzymatic degradations that frequently encountered while using natural molecules. Another challenge in design and preparation of functional molecular probes, especially nanometer scale probes, is water solubility. Because all biological systems use water as the medium to carry out chemical catalysis, cargo transportation, and force generation, water solubility is an essential problem that must be solved in the designing such molecular tools. The approach used by the principal investigator employs phosphorous chemistry to impart water solubility. The advantage of phosphorous chemistry is that polymeric probes can be prepared in organic media where most synthetic strategies can be applied and the resulting probes can function in water after activating the water solubility functions. These collective outcomes have accomplished the objective of this project, which is to make uniform polymeric probes that can measure molecular forces and transportation. Such molecular tools enable scientists to study molecular movements and force-generating mechanisms in situations where conventional instrumentations cannot be applied. In the future, it is planned that such molecular tools will be attached to receptors or key biomolecules under investigation for revealing important molecular mechanisms in biological systems.
