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[생체공학 부문] Shapes, Motions, and Forces in Cells
Jennifer H. Shin(신현정) Korean Society for Precision Engineering 2021 한국정밀공학회 학술발표대회 논문집 Vol.2021 No.11월
Cells in our body sense and respond to mechanical stimuli to regulate their physiological processes. These mechanical forces are exogenously imposed by various factors from the microenvironment of the tissue, regulating the biological responses of the cells. While normal cells in our body possess their own response strategies against moderate physicochemical stresses for homeostasis, pathological responses may be initiated to prompt disease conditions when the stress level falls below or goes above a critical threshold. Despite the importance of mechanical stresses in cellular physiology and pathology, the current focus of medicine largely ignores the physical basis of diseases. Pathological conditions such as cancer can be induced by an abnormality in the physical microenvironment, and the physical state of the cells can regulate their metastatic fate in the tumor mass. To understand the physiological behavior of the cells, it is crucial to develop pathologically relevant cell-based in vitro experimental models. In this work, we developed 2D and 3D cell-based models to visualize how stresses between adjacent cells and those between cells and the environment are produced in the clusters and how these stresses dictate the shapes and motions of the constituent cells. For quantitative analyses, we utilized particle image velocimetry (PIV), traction force microscopy (TFM), and monolayer stress microscopy (MSM) along with conventional biochemical assays and other phenotyping tools. We identified the active remodeling of stresses during the rearrangement of cell clusters. Using the simple 2D model, we unraveled the correlation among the shapes, motions, and physical stresses of the cells. In the context of cancer metastasis, we first identified the key factors that actively regulated the formation of the cellular aggregates and quantified the physical forces that would prevent the dissemination from occurring in the aggregates.
EFFECTS OF UNIFORM SHEAR STRESS ON THE MIGRATION OF VASCULAR ENDOTHELIAL CELL
신현정(Jennifer H. Shin),송석현(Sukhyun Song) 대한기계학회 2008 대한기계학회 춘추학술대회 Vol.2008 No.11
The migration and proliferation of vascular endothelial cells (VEC), which play an important role in vascular remodeling, are known to be regulated by hemodynamic forces in the blood vessels. When shear stresses of 2, 6, 15 dynes/㎠ are applied on mouse micro-VEC in vitro, cells surprisingly migrate against the flow direction at all conditions. While higher flow rate imposes more resistance against the cells, reducing their migration speed, the horizontal component of the velocity parallel to the flow increases with the flow rate, indicating the higher alignment of cells in the direction parallel to the flow at a higher shear stress. In addition, cells exhibit substrate stiffness and calcium dependent migration behavior, which can be explained by polarized remodeling in the mechanosensitive pathway under shear stress.
신현정(Jennifer H. Shin),김기중(Kijung Kim),한제현(Jehyun Han),박진성(Jin-Sung Park),박상후(Sanghoo Park),최원호(Wonho Choe) 한국가시화정보학회 2015 한국가시화정보학회 학술발표대회 논문집 Vol.2015 No.12
In this study, DBD (Dielectric Barrier Discharge) atmospheric pressure plasma source was utilized to deactivate wild type Salmonella strain. The bacterial motility was quantified based on the MSD (mean square displacement) to map the areal expansion of the moving bacteria. Also, to identify the relationship between motility and infectious activity of wild type Salmonella strain, the viability of the MCF-10A cells was accessed after the plasma-treated bacteria were co-incubated with the mammalian cells. The results show that the plasma treatment of as low as 10 seconds significantly reduces the motility of bacteria and the reduced motility correlates directly with the suppressed bacterial infection into the host cells.
이종 세포간 분리 현상 내 세포 이동성의 지배적 역할 규명
정현태(H. Jeong),Stephani Edwina Lucia,신현정(Jennifer H. Shin) Korean Society for Precision Engineering 2021 한국정밀공학회 학술발표대회 논문집 Vol.2021 No.11월
세포 분리 현상(Segregation Phenomenon)은 동일한 배아에서 시작된 세포가 다양한 특성을 갖는 조직으로 분화하는데 있어 기초적인 현상으로 제시되어 왔다. 세포의 분리 과정의 기본 원리는 주변 세포와 형성하는 동질 혹은 이질적인 세포 결합으로, 동질성을 띄는 세포들 간의 군집이 형성되고 이질성을 띄는 세포들 간에는 경계가 형성되며 나타난다. 이에 더불어, 동적 물질인 세포는 분열과 같은 자발적 요소와 화학 구배와 같은 주변 요소에 의해 다양한 이동성을 갖기 때문에, 이에 따른 경계 구조의 시공간적 변화 역시 필연적이다. 본 연구는 이종 세포간 분리현상 내의 세포 이동성의 역할을 파악하고자 이동 특성이 현저히 다른 두 상피세포종(HaCaT, MDCK)을 근아세포(C₂C12)와 공동배양 시 나타나는 분리현상의 차이를 관찰하였다. 체외 2 차원 공동배양 환경에서 두 상피세포종은 동일하게 근아세포가 형성한 망(Network) 형태 내부에 군집(Cluster)을 이룬 형태로 분리되었다. 하지만, 분리 이후 군집 내부의 HaCaT 과 MDCK 세포는 각각 본래의 이동 특성과 일치하는 급격한 회전운동과 점진적 확장운동을 나타냈다. 두 가지 운동특성은 근아세포 경계에서 상이한 반발력으로 나타났는데, 이를 정밀하게 분석하기 위해 본 연구진은 세포 역학적 지표의 정량화 기법인 TFM (Traction Force Microscopy)과 MSM (Monolayer Stress Microscopy)를 활용하였다. 이렇게 정량화된 근아세포의 전단응력 차이를 통해 회전 운동과 확장 운동이 서로 다른 충돌 메커니즘을 통해 근아세포에 반발력을 형성하게 됨을 규명하였다. 더 나아가, 충돌과정에서 주요한 힘을 형성할 수 있는 세포골격인 국소접착(Focal Adhesion)과 미오신(Myosin) 억제 실험을 통해서 이 메커니즘의 타당성을 증명하였다.