Jin Sung Park

Zigzag Turning Preference of Freely Crawling Cells

The coordinated motion of a cell is fundamental to many important biological processes such as development, wound healing, and phagocytosis. For eukaryotic cells, such as amoebae or animal cells, the cell motility is based on crawling and involves a complex set of internal biochemical events. A recent study reported very interesting crawling behavior of single cell amoeba: in the absence of an external cue, free amoebae move randomly with a noisy, yet, discernible sequence of ‘run-and-turns’ analogous to the ‘run-and-tumbles’ of swimming bacteria. Interestingly, amoeboid trajectories favor zigzag turns. In other words, the cells bias their crawling by making a turn in the opposite direction to a previous turn. This property enhances the long range directional persistence of the moving trajectories. This study proposes that such a zigzag crawling behavior can be a general property of any crawling cells by demonstrating that 1) microglia, which are the immune cells of the brain, and 2) a simple rule-based model cell, which incorporates the actual biochemistry and mechanics behind cell crawling, both exhibit similar type of crawling behavior. Almost all legged animals walk by alternating their feet. Similarly, all crawling cells appear to move forward by alternating the direction of their movement, even though the regularity and degree of zigzag preference vary from one type to the other.

In situ analysis of cisplatin binding to DNA: the effects of physiological ionic conditions

Platinum-based anti-cancer drugs form a major family of cancer chemotherapeutic agents. Cisplatin, the first member of the family, remains a potent anti-cancer drug and exhibits its clinical effect by inducing local DNA kinks and subsequently interfering with DNA metabolism. Although its mechanism is reasonably well understood, effects of intracellular ions on cisplatin activity are left to be elucidated because cisplatin binding to DNA, thus its drug efficacy, is modified by various ions. One such issue is the effect of carbonate ions: cisplatin binding to DNA is suppressed under physiological carbonate conditions. Here, we examined the role of common cellular ions (carbonate and chloride) by measuring cisplatin binding in relevant physiological buffers via a DNA micromanipulation technique. Using two orthogonal single-molecule methods, we succeeded in detecting hidden monofunctional adducts (kink-free, presumably clinically inactive form) and clearly showed that the major effect of carbonates was to form such adducts and to prevent them from converting to bifunctional adducts (kinked, clinically active). The chloride-rich environment also led to the formation of monofunctional adducts. Our approach is widely applicable to the study of the transient behaviours of various drugs and proteins that bind to DNA in different modes depending on various physical and chemical factors such as tension, torsion, ligands, and ions.

Trail networks formed by populations of immune cells

Populations of biological cells that communicate with each other can organize themselves to generate large-scale patterns. Examples can be found in diverse systems, ranging from developing embryos, cardiac tissues, chemotaxing ameba and swirling bacteria. The similarity, often shared by the patterns, suggests the existence of some general governing principle. On the other hand, rich diversity and system-specific properties are exhibited, depending on the type of involved cells and the nature of their interactions. The study on the similarity and the diversity constitutes a rapidly growing field of research. Here, we introduce a new class of self-organized patterns of cell populations that we term as ‘cellular trail networks’. They were observed with populations of rat microglia, the immune cells of the brain and the experimental evidence suggested that haptotaxis is the key element responsible for them. The essential features of the observed patterns are well captured by the mathematical model cells that actively crawl and interact with each other through a decomposing but non-diffusing chemical attractant laid down by the cells. Our finding suggests an unusual mechanism of socially cooperative long-range signaling for the crawling immune cells.

Focusing of light energy inside a scattering medium by controlling the time-gated multiple light scattering

The efficient delivery of light energy is a prerequisite for the non-invasive imaging and stimulating of target objects embedded deep within a scattering medium. However, the injected waves experience random diffusion by multiple light scattering, and only a small fraction reaches the target object. Here, we present a method to counteract wave diffusion and to focus multiple-scattered waves at the deeply embedded target. To realize this, we experimentally inject light into the reflection eigenchannels of a specific flight time to preferably enhance the intensity of those multiple-scattered waves that have interacted with the target object. For targets that are too deep to be visible by optical imaging, we demonstrate a more than tenfold enhancement in light energy delivery in comparison with ordinary wave diffusion cases. This work will lay a foundation to enhance the working depth of imaging, sensing and light stimulation.The use of a time-gated reflection matrix of a scattering medium, in particular via using singular value decomposition and injecting light into the largest time-gated eigenchannel, can lead to a more than tenfold enhancement in light energy delivery in comparison with ordinary wave diffusion cases.

Optical imaging featuring both long working distance and high spatial resolution by correcting the aberration of a large aperture lens

High-resolution optical imaging within thick objects has been a challenging task due to the short working distance of conventional high numerical aperture (NA) objective lenses. Lenses with a large physical diameter and thus a large aperture, such as microscope condenser lenses, can feature both a large NA and a long working distance. However, such lenses suffer from strong aberrations. To overcome this problem, we present a method to correct the aberrations of a transmission-mode imaging system that is composed of two condensers. The proposed method separately identifies and corrects aberrations of illumination and collection lenses of up to 1.2 NA by iteratively optimizing the total intensity of the synthetic aperture images in the forward and phase-conjugation processes. At a source wavelength of 785u2009nm, we demonstrated a spatial resolution of 372u2009nm at extremely long working distances of up to 1.6u2009mm, an order of magnitude improvement in comparison to conventional objective lenses. Our method of converting microscope condensers to high-quality objectives may facilitate increases in the imaging depths of super-resolution and expansion microscopes.

Label-free and live cell imaging by interferometric scattering microscopy

Despite recent remarkable advances in microscopic techniques, it still remains very challenging to directly observe the complex structure of cytoplasmic organelles in live cells without a fluorescent label.

Focusing of light energy inside a scattering medium by controlling the time-gated multiple light scattering (Conference Presentation)

To exploit photonics technologies for in vivo studies in life science and biomedicine, it is necessary to efficiently deliver light energy to the target objects embedded deep within complex biological tissues. However, light waves diffuse randomly inside complex media due to multiple scattering, and only a small fraction reaches the target object. Here we present a method to counteract the random diffusion and to focus ‘snake-like’ multiple-scattered waves to the embedded target. To realize this, we experimentally identified time-gated reflection eigenchannels that have extraordinarily large reflectance at a specific flight time where most of the multiple-scattered waves have interacted with the target object. By injecting light to these eigenchannels, we achieved more than 10-fold enhancement in light energy delivery compared to ordinary wave diffusion cases. This method works up to depths of approximately 2 times the transport mean free path at which target objects are completely invisible by ballistic optical imaging. This work will lay a foundation for enhancing the working depth of imaging, sensing, and light stimulation.