Biology subjects

Wangsrikhun, W.

Publications and source records attributed to Wangsrikhun, W..

3 recordsLinked to original sources

bioRxiv2026

PROPEL: a high-throughput shear-stress platform reveals organotypic thresholds in endothelial mechano-adaptation

Endothelial cells exhibit organotypic specialization, yet the tools to decode whether hemodynamic shear shapes this diversity across vascular beds have remained limited. Here we present PROPEL, a tubing-free, magnetic stirrer-driven platform that delivers programmable laminar shear stress (2 to 60 dyn/cm{superscript 2}) to multiple cell types in parallel within the confines of a standard Petri dish, with the modular flexibility to easily introduce different substrate geometries including 3D vessel formats. Using this platform, we profiled six human endothelial subtypes across static, low, intermediate, and high shear. Phenotypic profiling revealed subtype-specific thresholds for alignment, elongation, and Golgi-nuclear polarization, including a dissociation between elongation and polarization in dermal microvascular and saphenous venous endothelial cells at low shear. Bulk RNA sequencing showed conserved transcriptional programs that shift progressively with shear magnitude, including induction of mechanotransduction pathways alongside suppression of proliferative programs. Phenotype-informed transcriptional comparisons further linked alignment transitions to engagement of cytoskeletal and metabolic signatures. In addition to conserved responses, organotypic-specific responses were also observed. Together, these findings establish PROPEL as a scalable platform for multi-endothelial, multi-shear transcriptomic and phenotypic profiling, and reveal that endothelial cells engage shear adaptation along two organotypic axes--a threshold axis governing when a subtype responds and a signature axis governing which the shear stress response--with implications for vascular bed-specific disease susceptibility.

cell biology↗

bioRxiv2025

Mosaic pattern: lung functional heterogeneity at the alveolus level

Inhaled particles carrying pathogens, pollutants (e.g., microplastics, smoke), therapeutics, and diagnostics are increasingly relevant to public health, yet real-time tracking of aerosol transport in functional alveoli remains challenging. Here, we used the recently developed crystal ribcage to investigate aerosol transport in ex vivo lungs during active ventilation, obtaining the first real-time observations of single aerosol droplet transport and deposition in functional alveoli. We discovered deterministic heterogeneity at both intra- and inter-alveolar levels, with aerosol distribution forming a characteristic "mosaic" pattern in which only specific alveolar clusters received particles. The pattern was consistently formed in vivo during spontaneous breathing and ex vivo using both positive- and negative-pressure ventilation. This pattern was also consistent across a range of aerosols, including small molecules, nanobodies, nanoparticles, microplastics, therapeutics, and pathogens. Additionally, the pattern was observed in murine, porcine, and human lungs, and evolved from birth through aging in mice. The post-deposition stability of the pattern depended on particle type and lung age, lasting from a few minutes for small molecular weight particles to multiple days for cell-binding particles. These alveolar-level heterogeneities may uncover previously unrecognized biological and immunological heterogeneities associated with the mosaic pattern, including its role in postnatal lung development, susceptibility to inhaled airborne hazards such as pollutants and infectious agents, and early pathogenesis and response to inhaled therapeutics in respiratory diseases such as pneumonia, COPD, asthma, and lung cancer.

bioengineering↗

bioRxiv2025

Micromechanics of lung capillaries across mouse lifespan and in positive- vs negative-pressure ventilation

The lung undergoes continuous remodeling throughout normal development and aging, including changes to alveolar and capillary structure and function. While histological methods allow static analysis of these age-related changes, characterizing the changes that occur in response to mechanical stimuli remains difficult, particularly over a dynamic, physiologically relevant range in a functioning lung. Alveolar and capillary distension - the change in diameter of alveoli and capillaries, respectively, in response to pressure changes - is one such process, where dynamically controlling and monitoring the diameter of the same capillary or alveolus is essential to infer its mechanical properties. We overcome these limitations by utilizing the recently developed crystal ribcage to image the alveoli and vasculature of a functional mouse lung across the lifespan in postnatal (6-7 days), young adult (12-18 weeks), and aged (20+ months) mice. Using a range of biologically relevant vascular (0-15 cmH2O) and transpulmonary (3-12 cmH2O) pressures, we directly quantify vascular and alveolar distention in the functional lung as we precisely adjust pulmonary pressures. Our results show differences in age-related alveolar and vascular distensibility: when we increase transpulmonary alveolar or vascular pressure, vessels in postnatal lungs expand less and undergo less radial and axial strain, under each respective pressure type, suggesting stiffer capillaries than in older lungs. However, while vessels in young adult and aged lungs respond similarly to variations in vascular pressure, differences in elasticity start to emerge at the alveolar scale in response to transpulmonary alveolar pressure changes. Our results further indicate that differing effects of ventilation mode (i.e., positive vs negative) present themselves at the capillary level, with vessels under positive pressure undergoing more compression than when under negative-pressure conditions. These findings contribute both to the understanding of the functional changes that occur within the lung across the lifespan, as well as to the debate of ventilation effects on lung microphysiology.

physiology↗