arXiv subjects

Roger D. Kamm

Publications and source records attributed to Roger D. Kamm.

4 recordsLinked to original sources

arXiv2025

Self-localized ultrafast pencil beam for volumetric multiphoton imaging

The formation of organized optical states in multidimensional systems is crucial for understanding light-matter interaction and advancing light-shaping technologies. Here, we report the observation of a self-localized, ultrafast pencil beam near the critical power in a standard multimode fiber (MMF) and demonstrate its application in volumetric multiphoton imaging. We show that self-focusing in step-index MMFs, traditionally considered detrimental, can facilitate the formation of a nonlinear spatiotemporal localized state with a sidelobe-suppressed Bessel-like beam profile, exhibiting markedly improved stability and noise characteristics. By simply launching an overfilled on-axis Gaussian beam into a standard MMF, a high-quality ultrafast pencil beam can be generated through a self-localized process and readily integrated into an existing multiphoton point-scanning microscope. We apply this self-localized pencil beam to two-photon imaging of intact mouse enteric nervous systems, benchmarking with diffraction-limited Gaussian beams and outperforming conventional Bessel beams with reduced sidelobes and enhanced resilience to tissue-induced aberration. Finally, we monitor the transferrin uptake dynamics in a live human blood-brain barrier model by combining NAD(P)H-FAD-based metabolic phenotyping with minute-resolved 3D scans, revealing spatially and temporally resolved inter- and intra-cell heterogeneity. Our findings provide new insights into nonlinear dynamics of multidimensional optical systems and offer a promising approach for generating robust ultrafast pencil beams, enabling high-throughput 3D biosystem imaging to elucidate biological transport pathways and guide the design of therapeutics requiring cell-specific delivery.

physics.optics↗

arXiv2024

Deep and Dynamic Metabolic and Structural Imaging in Living Tissues

Label-free imaging through two-photon autofluorescence (2PAF) of NAD(P)H allows for non-destructive and high-resolution visualization of cellular activities in living systems. However, its application to thick tissues and organoids has been restricted by its limited penetration depth within 300 $μ$m, largely due to tissue scattering at the typical excitation wavelength (~750 nm) required for NAD(P)H. Here, we demonstrate that the imaging depth for NAD(P)H can be extended to over 700 $μ$m in living engineered human multicellular microtissues by adopting multimode fiber (MMF)-based low-repetition-rate high-peak-power three-photon (3P) excitation of NAD(P)H at 1100 nm. This is achieved by having over 0.5 MW peak power at the band of 1100$\pm$25 nm through adaptively modulating multimodal nonlinear pulse propagation with a compact fiber shaper. Moreover, the 8-fold increase in pulse energy at 1100 nm enables faster imaging of monocyte behaviors in the living multicellular models. These results represent a significant advance for deep and dynamic metabolic and structural imaging of intact living biosystems. The modular design (MMF with a slip-on fiber shaper) is anticipated to allow wide adoption of this methodology for demanding in vivo and in vitro imaging applications, including cancer research, autoimmune diseases, and tissue engineering.

physics.optics↗

arXiv2018

Balance of Mechanical Forces Drives Endothelial Gap Formation and May Facilitate Cancer and Immune-Cell Extravasation

The formation of gaps in the endothelium is a crucial process underlying both cancer and immune cell extravasation, contributing to the functioning of the immune system during infection, the unfavorable development of chronic inflammation and tumor metastasis. Here, we present a stochastic-mechanical multiscale model of an endothelial cell monolayer and show that the dynamic nature of the endothelium leads to spontaneous gap formation, even without intervention from the transmigrating cells. These gaps preferentially appear at the vertices between three endothelial cells, as opposed to the border between two cells. We quantify the frequency and lifetime of these gaps, and validate our predictions experimentally. Interestingly, we find experimentally that cancer cells also preferentially extravasate at vertices, even when they first arrest on borders. This suggests that extravasating cells, rather than initially signaling to the endothelium, might exploit the autonomously forming gaps in the endothelium to initiate transmigration.

q-bio.CB↗

arXiv2016

Effects of 3D Geometries on Cellular Gradient Sensing and Polarization

During cell migration, cells become polarized, change their shape, and move in response to various internal and external cues. Cell polarization is defined through the spatio-temporal organization of molecules such as PI3K or small GTPases, and is determined by intracellular signaling networks. It results in directional forces through actin polymerization and myosin contractions. Many existing mathematical models of cell polarization are formulated in terms of reaction-diffusion systems of interacting molecules, and are often defined in one or two spatial dimensions. In this paper, we introduce a 3D reaction-diffusion model of interacting molecules in a single cell, and find that cell geometry has an important role affecting the capability of a cell to polarize, or change polarization when an external signal changes direction. Our results suggest a geometrical argument why more roundish cells can repolarize more effectively than cells which are elongated along the direction of the original stimulus, and thus enable roundish cells to turn faster, as has been observed in experiments. On the other hand, elongated cells preferentially polarize along their main axis even when a gradient stimulus appears from another direction. Furthermore, our 3D model can accurately capture the effect of binding and unbinding of important regulators of cell polarization to and from the cell membrane. This spatial separation of membrane and cytosol, not possible to capture in 1D or 2D models, leads to marked differences of our model from comparable lower-dimensional models.

physics.bio-ph↗