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Biophysics, Bioengineering, and Nanomedicine

I. Real-Time Live-Cell Imaging of Intracellular Processes

II. Functional Abiotic Nanosystems for Intracelluar Prostheses

 

 

Real-Time Live-Cell Imaging of Intracellular Processes

     The ability to examine intracellular structure and processes in live cells is fundamental to understanding phenomena underlying diseases and pathways for intervention. To address issues of clinical importance (chosen in conjunction with colleagues in the USC Keck School of Medicine) we are embarked upon studies utilizing optical microscopy, spectroscopy, and imaging of live cells. To find out more, please click on the categories below or click here to read our paper.

 

I. Epifluorescent and Confocal Microscopy

II. Near-Field Optical Microscopy

III. Real-Time Imaging of Cells Under Stress

 

Functional Abiotic Nanosystems for Intracellular Prostheses


The Concept of Functional Abiotic Nanosystem (FAN):

    To examine intracellular processes and to create intracellular prostheses, we have introducted the concept of Functional Abiotic Nanosystems (FAN). FAN's are nanoscale systems that perform an active function and consist of appropriately engineered composites of nanoscale building blocks such as organic/biochemical (but abiotic) nanoparticles or inorganic nanocrystals (such as quantum dots, quantum rods, etc.). The FAN's provide higher level functions beyond, for example, the current simple uses of individual quantum dots as imaging labels or local heaters. An implementation of the FAN concept is the modulation of transmembrane potential of neuronal cells through its strategic placement near ion channels. This is shown schematically in figure 1 where the FAN is activated to provide change in local electric field. The active function is to induce channel opening upon external stimulation (e.g. via photon). In this way, a FAN acts as a nanoscale intracellular prosthesis.


Fig. 1: Schematic showing strategic placement of FAN near ion channel protein to induce gate opening upon external stimulation.

 

The first application of FAN being investigated is potentially restoring vision for individuals with blindness due to the loss of photoreceptors in an otherwise intact retina. To learn how we propose to achieve this, please read on.

 

Functional Abiotic Nanosystem (FAN) as a Nanoscale Photodiode for Retinal Prosthesis

    "This non-invasive electrical stimulation using embedded FAN may offer a variety of oppotunities ranging from probing fundamental intracellular electric processes to endowing/restoring light sensitivity to retinal neurons (such as the retinal ganglion cells) and serving as nanoscale devices for visual prosthesis." [1] A FAN as a cellular-prosthesis for retinal stimulation is shown schematically in figure 2. FANs designed to act as nanoscale photodiodes are to be embedded directly in the plasma membrane of retinal ganglion cells (RGCs). Upon light excitation, the induced photovoltage created by the FAN's may be tailored to modulate the transmembrane potential sufficiently to open nearby ion channels. Such opening can trigger action potential which travel down the optic nerve to the visual cortex and lead to sensation of vision.

    The idea of stimulating retinal ganglion cells in patients blind due to loss of photoreceptors is being actively pursured by a number of groups including a team of researchers at USC (BMES), including us. However, all such efforts use microelectronics based macroscopic implants (Fig. 3) much like the cochlear implants used to restore hearing in the deaf. Employing engineered photovoltaic FAN's embedded directly in the retinal ganglion cells, as we are embarked upon, would obviate the need for such macroscopic implants, requiring only an injection of FAN's into the eye. A major advantage of our approach is its minimally invasive nature.


Fig.2 Nanoscience based paradigm to restore vision: Direct stimulation of retinal ganglion cells using trans-membrane embedded photosensitive Functional Abiotic Nanosystem (FAN).

 

Fig.3 Current paradigm to restore vision: stimulate ganglion cells using implanted macroscopic electrodes.

See our paper for more details

S. Lu and A. Madhukar, "Cellular prostheses: functional abiotic nanosystems to proble, manipulate, and endow functions in live cells." Nanomedicine: Nanotechnoloty, Biology, and Medicine, 6, 409-418 (2010) [CLICK HERE]

References:
[1] Siyuan Lu, Ph.D. Dissertation, chapter 7, pp 337, University of Southern California, 2006.



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