During the past Ph. D. course, my experimental studies had been focused on complex spiral waves with "line-defects" revealed in a Belousov-Zhabotinsky (BZ) chemical reaction. The spiral wave in complex oscillatory media are far more complicated than the much studied simple spiral waves in simple oscillatory or excitable media. Among others, the most salient feature of a complex periodic spiral wave is the existence of line defects across which the phase of the local oscillation changes by a multiple of 2 &pi .In fact, the line defects are an essential property of complex periodic spiral waves, just as the topological (phase) singularity is a fundamental property of a simply periodic P-1 spiral wave. A few later, strikingly similar example of complex spiral waves having line defects was observed in cardiac cell cultures. This observations supports the notion that line defects are a generic feature in a broad class of complex periodic systems including biological systems. Our comprehensive review paper regarding our experimental results on complex oscillatory BZ spiral waves were published in [ Phys. Rev. E (2006)].
Figure 1. Snapshot images of spiral waves (left) and processed images revealing their associated line-defects (right) observed in a BZ reaction-diffusion system: (a) P-1 spiral wave with no line defect; (b) continuous P-2 spiral wave and associated line-defect with a shape of P-1 spiral wave; (c) discontinuous P-2 spiral wave and associated line-defect with a shape different from P-1 spiral. The processed images is now revealing the existence of line defects (narrow black strips) and domains of P-1 (black) and P-2 (bright).
Currently, I am interested in two differnt biological issues, one is to understand physical properties of cell motility in relation with focal adhesions (FAs), and the other is a field of single molecule biophysics studying the direct interaction between DNA-anticancer drugs, or DNA-proteins.
A series of recent studies augments the role of glia as regulatory agents
of neuronal activity, undertaking active roles in brain computation.
Intercellular and extracellular calcium kinetics are believed to be an
important mediator for the interplay among neurons and glia. In mature
of neuron-glia co-culture systems, populations of neurons often exhibit
globally synchronized fast "calcium spikes" that are accompanied by
electrical bursts of action potentials. While the glia in the same culture
systems do often show slower "calcium wave" activities that possibly
modulate the neuronal activity. We examine the property of these slowly
propagating calcium waves in pure glia networks under various
pharmacological conditions and with different extrinsic stimulations.
Figure 2. Small irregular wavelets emerging in the wake of some dominant pacemakers observed in a layer of purely cultured astrocytes: (a) sequential images showing a spontaneously generated calcium wave (96-99 sec) and small irregular wavelets circulating along local recurrent network, and (b) local timeseries obtained from two different sites (A and B) in (a) This experiments were conducted in extracellular free calcium and magnesium buffer condition.
Microglia are a type of glia cell, acting as representatives of
the immune system in the brain. This cell is very motile, constantly
moving to destroy pathogenes and to remove damaged neurons and plaques.
In this process, dynamic assembly and disassembly of focal adhesions
(FAs) plays a central role. FAs are large, dynamic
complex protein assembly through which cytoskeleton of cell inside
directly connect to extracellular matrix and path to transmit
mechanical force and regulatory signals. Currently, we have investigating
on (i) the relation of a directional motion of single microglia and
dynamic process of FAs,
and (ii) collective dynamics in population of microglia through
cell-to-cell signaling in the absence of external signal.
Figure 3. A typical morphology of cultured microglia with a cell body of round shape and a long tail (left and center), and a thin trail pattern formed spontaneously through cell-to-cell interaction in population of cultured microglia (right).
Single molecule biophysics has been well known as a powerful technique to understand physical principles behind a wide range of biological phenomena. Recently, we have investigated on salt dependent activity of cisplatin observed through micromanipulation of a single bare DNA molecule with magnetic tweezers. Cisplatin, a potent mutagenic anti-cancer drug, induces a DNA kink by intra- or inter-strand crosslinks, especially at two neighboring purine sites, which induces apotosis of proliferating cancer cells. Now, we have studying on modification in chromatin structure by irreversibly crosslinking DNA and histones to understand an anti-cancer activity of cisplatin in more realistic in vivo state - DNA compacted by wrapping the histons. Our studies shed light on understanding the efficacy of drugs that induce conformational changes in DNA.
Figure 4. Design of temperature controlled magnetic tweezers system: The sampled chamger was made by stacking an ITO plate on a cover glass. A DC power supply was connected to the plate to generate ohmic heat and a water bath circulated water at a persent temperature through the silicon tubing to warm the oil-immersion objective. DNA molecules attached to a magnetic bead were fixed in the sample chamber and manipulated with a pair of magnets while imaged with a bright field microscope.