Learning from Cells for Transport at Micron Scale

Abstract:

The realization of a robust infrastructure that enables simultaneous transport of many micron and smaller sized particles will have a transformative impact on a vast range of areas such as medicine, drug development, electronics, and bio-materials. In this proposal, cyberphysical, scientific as well as technological principles will be developed for realizing a hierarchical architecture for control,  monitoring and design of an engineered transport infrastructure for micron scaled particles.  Such a transport network will be realized using bio-molecular components. Components for monitoring and control will be enabled by a modern feedback control framework, fluorescence microscopy and optical trapping principles. This cellular-scale transport network will form a testbed to assess and verify proposed cyberphysical scientific and technological principles and tools. This assessment will require co-designing algorithmic, control, signal analysis, and physical layers which encompasses the vision of the CPS program. Furthermore, it will enable testing of new hypotheses on modalities of intracellular transport with access from single-molecule scale to the global scale.

Daunting challenges from the underlying highly uncertain and complex environments impede enabling robust and efficient transport systems at micro-scale. Motivated by robust and efficient transport in biological cells, this work proposes an efficient and robust engineered infrastructure for transporting micron/molecular scale cargo using biological constructs. For probing and manipulating the transport network, the proposal envisions strategies for coarse and fine resolution objectives at the global and local scales respectively. At the fine scale of monitoring and control, scarce and expensive physical resources such as high resolution sensors have to be shared for interrogation/control of multiple carriers. In this proposal, the principles for joint control, sensor allocation and scheduling of resources to achieve enhanced performance objectives of a high resolution probing tool, will be developed. A modern control perspective forms an essential strategy for managing multiple objectives.   At the global scale, entire traffic will be monitored to arrive at real-time and off-line inferences on traffic modalities. Associated principles for dynamically identifying and tracking clusters of carriers and their importance will be built. This categorization of physical elements and their importance will determine the dynamic allocation of computational resources. Associated study of trade-offs will guide a combined strategy for  allocation of computational resources and gathering of information on physical elements. Methods based on the reconstruction of graph topologies for reaching inferences that are suited by dynamically related time trajectories for the transportation infrastructure will be developed. The research proposed is transformative as it will enable a new transport paradigm at the cellular scale, which will also provide unique insights into intracellular transport where it will be possible to investigate multiple factors under the same experimental conditions.  In summary, the main technical objectives  for bioconstructs-based microscale transport (i) develop cyber-physical platform comprised of manipulation and sensing using optical fields, (ii) develop cyber-physical principles  for control with resource allocation constraints and develop  co-ordination mechanisms for transport by multiple agents, and (iv) enable  discovery of intra-cellular transport mechanisms.

Also under the proposal, a collaborative effort with Science Museum of Minnesota, a bench will be developed with the aim of providing an immersive experience of cyberphysical approaches to experimentation for intracellular transport.. The proposal includes an educational platform that will have  the essential ingredients of the cyberphysical tool integrated into a  course for  senior  undergraduate and first year graduate students. The components used to realize the engineered cellular scale transport network use microtubules as tracks and motor-proteins as carriers; components employed by cells for transport.   Thus, proposed research will impact bio-molecular research with possible   important long-term implications for the understanding and treating of spinal cord injuries and a family of neurodegenerative diseases.