Research

Cellular and Vascular Mechanobiology

Investigating how acoustic forces regulate vascular biology, mechanosensitive signaling, and immune-cell function.

Our laboratory investigates how microbubble (MB)-generated mechanical forces regulate vascular biology. We showed that ultrasound excitation just above MB resonance maximizes vessel wall shear stress and regulates the enrichment of inflammatory pathways responsive to wall shear stress (Nature Communications 2024).

Mechanoregulation of Immune Cell Trafficking. a) Microbubble resonant effects in brain capillaries lead to high wall share stress (WSS). b) High WSS leads to upregulation of inflammatory transcripts (e.g., ICAM-1) in the endothelial cells of BBB.

Crucially, we demonstrated that operating below MB resonance opens the blood-brain barrier with lower inflammatory signaling, challenging the conventional view that higher frequencies are inherently safer in ultrasound driven MB dynamics. Conversely, tuning ultrasound near resonance maximizes shear stress to enhance CAR T-cell trafficking into aggressive brain tumors.

This work established for the first time that ultrasound frequency and MB resonance can be tuned to harness immuno-mechano-biological responses, creating molecular, not just spatial, therapeutic windows for targeting central nervous system diseases

Protein expression analysis in mouse brain tissue. A Representative fluorescent microscopy data of ICAM-1 expression at 8 h after MB-FUS treated with 150 kPa. Red, ICAM-1; green, CD31. B Quantification of ICAM-1 expression treated with 150 kPa (upper) and 175 kPa (lower) pressure (n = 4 for 150kPa group, n = 6 for 175 kPa group) (p = 0.011 for 150 kPa group, p = 0.006 for 175 kPa group). C Representative fluorescent microscopy data of IBA-1 expression at 8 h after MB-FUS treated with 150 kPa. Green, IBA-1; blue, DAPI. D Quantification of IBA-1 expression treated with 150 kPa pressure (n = 4, p = 0.049). Measurements were taken from distinct samples. Plots show means ± SD. P values were determined by two-tailed paired t tests. *P ≤ 0.05, **P ≤ 0.01.
Enhanced infiltration of epidermal growth factor receptor variant III (EGFRvIII) CAR-T cells in SB28 Glioma tumor model after sonication with 1.5 MHz frequency. Left: Schematic illustration of CAR-T cells infiltration to brain tumor with MB-FUS using different ultrasound frequencies. Right: Quantification of the percentage of CAR T cells in all live cells in SB28 glioma tumor when treated with 150 kPa (left, n = 5) and 175 kPa (right, n = 4 for non-FUS and 0.5 MHz group, n = 5 for 1.5 MHz group) (150 kPa: non-FUS vs 0.5 MHz, p = 0.009; non-FUS vs 1.5 MHz, p = 0.002; 175 kPa: non-FUS vs 1.5 MHz, p = 0.049).