Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow.
Proc Natl Acad Sci U S A
; 112(51): E7039-47, 2015 Dec 22.
Article
em En
| MEDLINE
| ID: mdl-26663913
ABSTRACT
Cavitation with bubble-bubble interaction is a fundamental feature in therapeutic ultrasound. However, the causal relationships between bubble dynamics, associated flow motion, cell deformation, and resultant bioeffects are not well elucidated. Here, we report an experimental system for tandem bubble (TB; maximum diameter = 50 ± 2 µm) generation, jet formation, and subsequent interaction with single HeLa cells patterned on fibronectin-coated islands (32 × 32 µm) in a microfluidic chip. We have demonstrated that pinpoint membrane poration can be produced at the leading edge of the HeLa cell in standoff distance Sd ≤ 30 µm, driven by the transient shear stress associated with TB-induced jetting flow. The cell membrane deformation associated with a maximum strain rate on the order of 10(4) s(-1) was heterogeneous. The maximum area strain ([Formula see text]) decreased exponentially with Sd (also influenced by adhesion pattern), a feature that allows us to create distinctly different treatment outcome (i.e., necrosis, repairable poration, or nonporation) in individual cells. More importantly, our results suggest that membrane poration and cell survival are better correlated with area strain integral ([Formula see text]) instead of [Formula see text], which is characteristic of the response of materials under high strain-rate loadings. For 50% cell survival the corresponding area strain integral was found to vary in the range of 56 â¼ 123 µs with [Formula see text] in the range of 57 â¼ 87%. Finally, significant variations in individual cell's response were observed at the same Sd, indicating the potential for using this method to probe mechanotransduction at the single cell level.
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01-internacional
Base de dados:
MEDLINE
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article