Nano- and Bio-Electronics: Semiconductor-enabled exploration of bioelectric properties of organelles
Abstract
Intracellular signaling is the basis or the biological activity and cellular processes. Traditionally, our knowledge about intracellular dynamics has been limited to biochemical and transcriptional pathways. However, studies over the last several decades have demonstrated that single cells also use electrical and mechanical signals for processing intracellular information. These signals can be manifested as rapid voltage changes across intracellular membranes or as localized force generation within cytoskeleton network. Additionally, the intracellular electrical and mechanical properties and dynamics tend to be rather inhomogeneous. For instance, action potentials in nerve cells are typically initiated at the axon hillock and the resultant voltage pulse travels down the myelinated axon to the nerve terminal. To understand and then modulate intracellular biophysical activity, tools that arc minimally invasive, display high spatiotemporal resolution, and exhibit large signal-to-noise are necessary. Although optical methods have attempted to address these challenges for decades, their application has been limited to only a few areas; such as plasma membrane voltage recording, changes in intracellular ion concentrations, force mapping near focal adhesions, and optogenetic control of cell excitability. Implantable electronics have also been used in numerous cellular modulations. While these tools have been clinically beneficial in the intended patient populations, the fundamental mechanisms by which they arc able to elicit therapeutic effects at the cellular and subcellular levels remain elusive. Our proposed research aims to address these fundamental questions by investigating the bioelectric dynamics of individual organelles and their networks with nanoscale silicon-based electronic, optoelectronic and thermal devices, which would all yield changes of the bioelectric environment near single organelles. We 1,vill target mitochondria, cytoskeletal filaments, and endoplasmic reticulum (ER), and we will evaluate the unknown bioelectric signatures in the frequency domain for these subcellular components. To realize the central goal or the project, we will synthesize and characterize nanoscale silicon materials that arc uniquely suited for interlacing with intracellular components. We will explore different surface chemistry for silicon nanostructures Lo promote their internalization and subsequent subcellular targeting. We will construct silicon-based nanoscale capacitor, photogalvanic cell, and heater as wireless, localized subcellular simulators inside single cells. We will use optical imaging and various biological assays lo study how optical stimulations affect local bioelectric behavior or organelles. Finally, we will perform simulations with coarse-grained molecular dynamics method, which is capable of modeling the dynamics of biomolecules at various granularity levels. I expect this work, if successful, can address a wide range or scientific questions in intracellular signaling, organelle dynamics, and spatiotemporal (up lo nanometer spatial resolution and microsecond temporal resolution) organization or bioelectric pathways; all being enabled by internalized silicon-based bioelectric modulations. Additionally the bioelectric mechanisms being uncovered in this work will become powerful new "building blocks" for efforts in the emerging field of synthetic biology - representing a ne1,v physical tool ! or biologists and bioengineers. Finally, beyond gaining fundamental understanding, our work may enable new non-invasive treatment of ccr1ain diseases that can meet the Army need, such as large area wound healing, and traumatic brain injury.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 11, 2018
- Source ID
- W911NF1810042
Entities
People
- Bozhi Tian
Organizations
- Army Contracting Command
- United States Army
- University of Chicago