Cell migration is an important process both in physiological and pathological conditions. Migrating cells in vivo respond to various extracellular environmental factors and change their migratory behavior. Thus, it is important to take into account extracellular environmental factors in studies on cell migration. This study specifically focused on fibroblast migration in a three-dimensional microenvironment. We fabricated a polydimethylsiloxane cell culture substrate with intersecting grooves as a model to mimic a feature of the complex porous microenvironment experienced by fibroblasts in vivo. The sizes of the grooves allowed fibroblasts to penetrate into the grooves. The effects of branched grooved structures on cell migration, and on cellular organization of the actin filaments and phosphorylated myosin light chain, were analyzed. Fibroblasts migrated along intersecting lattice grooves that were 5 μm wide, 13 μm deep, and spaced 10 μm apart. Analysis of the cellular distribution of actin filaments and phosphorylated myosin light chain demonstrated two effects of the intersecting grooved structure on actin cytoskeletal organization in the fibroblast. One was the enhancement of filopodia protrusions into the branched groove at the junction, and the other was the formation of stress fibers to cross the opening of the junction. These results suggest that the filopodia protrusions are guided by the groove and are followed by the cytoplasmic protrusion, then the rear of the cell retracts due to stress fiber contraction, leading to fibroblast guided migration in the branched intersecting groove.

Keywords

Three dimensional microenvironment, Intersecting grooves, Filopodia, Stress fiber, Phosphorylated myosin light chain, Fibroblast, Polydimethylsiloxane

Paper information

Hiromi MIYOSHI, Miki NISHIMURA, Yutaka YAMAGATA, Hao LIU, Yasuyoshi WATANABE, Michiko SUGAWARA, “Cell migration guided by a groove with branches”, Journal of Biomechanical Science and Engineering, Vol.12, No.1 (2017), p.16-00613. doi:10.1299/jbse.16-00613. Final Version Released on March 31, 2017, Advance Publication Released on February 07, 2017.

Prediction of rupture status in cerebral aneurysms remains challenging for clinicians, and the important rupture indicator (wall shear stress, WSS) is controversially discussed. Recent studies report that flow instabilities appear to play an influential role in the evolution and rupture of aneurysms and it is strongly correlated with both geometries and inlet flow rate waveforms. However, how frequency harmonics in inlet flow rate waveforms influence the flow instabilities and hence WSS fluctuations in cerebral aneurysms are still unclear. In this study, we used a computational fluid dynamic (CFD) model of anatomically realistic cerebral aneurysms combining with Fourier series and power spectral density (PSD) analysis to investigate the association between inflow waveform's harmonic frequencies and flow fluctuations in terminal cerebral aneurysms. Our simulated results demonstrated that there exists a harmonic frequency dependency in inlet flow rate waveforms inherently associated with flow instabilities in cerebral aneurysms: low-frequency harmonics play a crucial role in causing significant WSS fluctuations. This is partly explained by that the low-frequency harmonics govern a primary local adverse pressure gradient at late systole during flow deceleration, which induces flow instabilities while giving it sufficient time to develop into flow instabilities whereas high-frequency harmonics do not but decay rapidly. This implies that flow fluctuations in cerebral aneurysms may be of some robustness, dependent mainly on the primary harmonic frequency initiated by heart contraction but against unpredictable high-frequency perturbations in the inflow waveforms.

Keywords

Cerebral aneurysm, Flow instability, Wall shear stress (WSS), Computational fluid dynamic (CFD)

Paper information

Lijian XU, Atsushi SAITO, Yoko YOKOYAMA, Kenya SATO, Tatsuya SASAKI, Ryuhei YAMAGUCHI, Michiko SUGAWARA, Hao LIU, “Low-frequency harmonics in inlet flow rate play a crucial role in inducing flow instabilities in terminal cerebral aneurysms”, Journal of Biomechanical Science and Engineering, Vol.11, No.3 (2016), p.16-00117. doi:10.1299/jbse.16-00117. Final Version Released on September 15, 2016, Advance Publication Released on April 26, 2016.

A computational study of effects of vessel dynamics and compliance on coronary artery hemodynamics with / without stenosis is presented. The coronary artery hemodynamics with stenosis has been a main subject as one of the major cardiovascular diseases induced by atherosclerosis; most computational models assume that the vessel movement and deformation are negligible (Zeng, et al., 2003; Kim, et al., 2010). However, it is till unclear whether the hemodynamic characteristics owning to vessel dynamics and compliance is clinically significant or not particularly under pathological conditions. In this study, we aim at investigating the hemodynamic effects of the vessel dynamics and compliance in right coronary artery under healthy situation without stenosis as well as under diseased conditions with stenosis. We constructed a three-dimensional geometric model of the right coronary artery based on X-ray angiographic images, in which both vessel movement and deformation were taken into account. A specific volumetric flow rate was employed as a boundary condition imposed on inlet. Furthermore, we carried out an extensive study on the inlet waveform dependence and the effects of the vessel compliance on coronary hemodynamics. Our results demonstrate that the conventional assumption on 'rigid' artery models holds only in the cases of normal coronary arteries but fails for stenosed coronary arteries where the vessel dynamics and compliance do extend significant influence on distributions of the oscillatory shear indices (OSIs). Moreover, we find that the effects of vessel dynamics and compliance on coronary hemodynamics seem to be independent of both inlet boundary conditions and the vessel compliance.

Keywords

Coronary artery, Compliance, Hemodynamics, Stenosis, Computational biomechanics

Paper information

Takashi FUJIWARA, Fuyou LIANG, Ken-ichi TSUBOTA, Michiko SUGAWARA, Yu-qi FAN, Hao LIU, “Effects of vessel dynamics and compliance on human right coronary artery hemodynamics with / without stenosis”, Journal of Biomechanical Science and Engineering, Vol.10, No.2 (2015), p.15-00015. doi:10.1299/jbse.15-00015. Final Version Released on May 29, 2015, Advance Publication Released on April 28, 2015.