Research
Our current research are focused on the following topics.
- Cancer biomechanics and biotransport
- Cell migration
- Development of biomimetic materials for cell migration
- Biomechanics of microcirculation
- Design of cell separation/sorting/alignment and cell diagnosis
- Biorheology
- Numerical modeling
- Coarse-grained molecular dynamics
- Bioengineering for diagnosis/surgical operation/medical tools
Cancer biomechanics and biotransport
Cancer cells reproduce endlessly and grow abnormally. The relationship between intracellular substance tranport and cancer drug ressistance or cell death (apoptosis) has attracted particular attention. In this study, we focus on the relationship between mechanical stimuli and intracellular material transport, measuring the movement and localization of intracellular proteins in real time. By combining experimental observations with mechanical model analysis, we aim to clarify the relationship between mechanics, intracellular material transport phenomena, and diseases, ultimately contributing to the development of new therapeutic applications.
Cell migration
Cell migration is a fundamental phenomenon in cancer metastasis and tissue/organ development. In this study, we focus on elucidating the mechanism of directional cell migration. Specifically, we aim to clarify the crosstalk between single-cell and collective-cell behaviors under different substrate conditions and intracellular protein dynamics. By gaining insights into wound healing and tissue formation, we seek to contribute to advancements in regenerative medicine.
Development of biomimetic materials for cell migration
Cells respond to the mechanical properties of their environment by altering their metabolic activity as well as their proliferation and differentiation states. To elucidate the mechanism of cellular force field sensing, we are developng novel cell culture substrates that mimic in vivo tissues using polymer hydrogels with controllable physical properties. Our goal is to establish cell manipulation techniques, such as the spontaneous localization of heterogeneous cells and the inhibition of cancer cells, by designing extracellular mechanical fields. We ultimately aim to apply these advancements to cancer treatment, regenerative medicine, and artificial organs.
Biomechanics of microcirculation
The microciculatory blood flow can be well estimated as Stokes flow due to almost inertialess. In such flow field, a deformable spherical particle tends to migrate toward the channel center, the so-called "axial migration". Based on the principle of fluid mechanics, we investigate the cellular scale blood flow, and seek to clarify the mechanical background of various phenomena regarding convective mass transport in microcirculations.
Design of cell separation/sorting/alignment and cell diagnosis
Microfluidics techniques allow us to reduce the complexity and costs of clinical applications by using small amount of blood samples. The knowledge of intrinsic phenomena in microfluidic devices can be utilized for label-free cell alignment/sorting/separation techniques to diagnose precisely patients with haematologic disorders, or for the analysis of anticancer drug efficacy in cancer patients. For novel microfluidic techniques, we study the detailed hydrodynamic interaction between the cell and background fluid in confined microchannels.
Biorheology
Since human blood is a dense suspension consisting of 55% fluid (plasma) and 45% blood cells, with over 98% of the cells being red blood cells (RBCs), hydrodynamic interactions of individual RBCs are of fundamental importance for haemorheology. We seek to clarify how the single-cell behaviour relates to the behavior in suspensions and then rheology. Based on this knowledge, we will gain insights into controlling suspension rheology (e.g., viscoelasticity) of soft particles.
Numerical modeling
Lipid bilayer membranes, consisting of a series of opposing phospholipids arranged in a tow-dimensional (2D) fluid crystalline assembly with about 5-nm thickness, are a common and fundamentally important structure in mammalian cell. Such fluid deformable surfaces exhibit a solid-fluid duality, resulting in unique and complex mechanical characteristics where in-plane fluidity and elasticity can emerge simultaneously. We investigate this viscoelasticity by building hydrodynamic equations of bilayer membranes. Through this attempt, we also build not only constitutive equation of lipid bilayer membrane but also a concept spanning from nano-scale dynamics to macroscale behaviours/properties/functions.
Selected papers
Coarse-grained molecular dynamics
Thrombi form a micro-scale fibrin network consisting of an interlinked structure of nanoscale protofibrils, resulting in haemostasis. We seek to clarify how the nanoscale protofibril dynamics affect the formation of the macro-scale fibrin clot and thus its mechanical properties. For this issue, we have proposed a minimal mesoscopic model for protofibrils based on Brownian dynamics and performed numerical simulation of protofibril aggregation. The model analysis is useful to understand the relationship between individual protofibril behaviours and the macro-scale mechanical response of fibrin clots, including the fibrous network structure.
Selected papers
Bioengineering for diagnosis/surgical operation/medical tools
Though it is rare, congenital tracheal stenosis (CTS) is one of the most severe tracheal disorders and is commonly the result of complete tracheal rings of cartilage that vary in location, length, and the severity of luminal narrowing. To help to make therapeutic decisions about surgery and evaluate breathing performance or quality of life both in preoperative and postoperative patients, we perform simulations of airflow using subject-specific airway models were constructed from subjects' CT data.
