Kimmy Tran

Bio: Kimmy Tran is an academic researcher. The author has contributed to research in topics: Cell migration & Extracellular matrix. The author has an hindex of 1, co-authored 1 publications receiving 2 citations.

Collagen Matrices Mediate Glioma Cell Migration Induced by an Electrical Signal

Abstract: Glioma cells produce an increased amount of collagen compared with normal astrocytes. The increasing amount of collagen in the extracellular matrix (ECM) modulates the matrix structure and the mechanical properties of the microenvironment, thereby regulating tumor cell invasion. Although the regulation of tumor cell invasion mainly relies on cell–ECM interaction, the electrotaxis of tumor cells has attracted great research interest. The growth of glioma cells in a three-dimensional (3D) collagen hydrogel creates a relevant tumor physiological condition for the study of tumor cell invasion. In this study, we tested the migration of human glioma cells, fetal astrocytes, and adult astrocytes in a 3D collagen matrix with different collagen concentrations. We report that all three types of cells demonstrated higher motility in a low concentration of collagen hydrogel (3 mg/mL and 5 mg/mL) than in a high concentration of collagen hydrogel (10 mg/mL). We further show that human glioma cells grown in collagen hydrogels responded to direct current electric field (dcEF) stimulation and migrated to the anodal pole. The tumor cells altered their morphology in the gels to adapt to the anodal migration. The directedness of anodal migration shows a field strength-dependent response. EF stimulation increased the migration speed of tumor cells. This study implicates the potential role of an dcEF in glioma invasion and as a target of treatment.

Mechanical characterization of erythrocyte-derived optical microparticles by quantitative phase imaging and optical tweezers

Abstract: We have fabricated constructs from erythrocytes that contain the near-infrared (NIR) dye, indocyanine green (ICG). We refer to these constructs as NIR erythrocyte mimicking transducers (NETs). Mechanical properties of NETs can play an important role in the circulation kinetics and biodistribution of these particles. We characterize the mechanical properties of erythrocytes, hemoglobin-depleted erythrocytes ghosts (EGs), and micron-sized NETs (μNETs) through analysis of membrane fluctuations measured by quantitative phase imaging, and forces associated with membrane tethers pulled by optical tweezers. EGs were prepared from erythrocytes by hypotonic treatment. μNETs were prepared through hypotonic loading of 25 μM ICG into EGs. Quantitative phase images were obtained by a common-path interferometric phaseshifting system. Approximating the membrane as a sheet of springs, we estimated the stiffness of the membrane of erythrocytes, EGs, and µNETs as 3.0 ± 0.6 pN/μm, 6.5 ± 2.1 pN/μm, and 8.0 ± 2.1 pN/μm. Optical tweezers experiments yielded a similar trend. Differences in membrane stiffness suggest that the circulation dynamics of μNETs may be altered as compared to native erythrocytes.

Intravital Vascular Phototheranostics and Real-Time Circulation Dynamics of Micro- and Nanosized Erythrocyte-Derived Carriers

Abstract: Erythrocyte-based carriers can serve as theranostic platforms for delivery of imaging and therapeutic payloads. Engineering these carriers at micro- or nanoscales makes them potentially useful for broad clinical applications ranging from vascular diseases to tumor theranostics. Longevity of these carriers in circulation is important in delivering a sufficient amount of their payloads to the target. We have investigated the circulation dynamics of micro (∼4.95 μm diameter) and nano (∼91 nm diameter) erythrocyte-derived carriers in real time using near-infrared fluorescence imaging, and evaluated the effectiveness of such carrier systems in mediating photothermolysis of cutaneous vasculature in mice. Fluorescence emission half-lives of micro- and nanosized carriers in response to a single intravenous injection were ∼49 and ∼15 min, respectively. A single injection of microsized carriers resulted in a 3-fold increase in signal-to-noise ratio that remained nearly persistent over 1 h of imaging time. Our results also suggest that a second injection of the carriers 7 days later can induce a transient inflammatory response, as manifested by the apparent leakage of the carriers into the perivascular tissue. The administration of the carriers into the mice vasculature reduced the threshold laser fluence to induce photothermolysis of blood vessels from >65 to 20 J/cm2. We discuss the importance of membrane physicochemical and mechanical characteristics in engineering erythrocyte-derived carriers and considerations for their clinical translation.

Bioelectricity: A Top-Down Control Model to Promote More Effective Aging Interventions

Abstract: Aging is a complex, multifaceted process that affects all organisms, characterized by functional decline and increased risk of death. Although the molecular and cellular basis of aging has been extensively studied, the roles of bioelectricity, biochemical gradients, and biomechanical gradients in this process remain less understood. This review investigates the current knowledge concerning these factors and their influence on aging at molecular, cellular, and whole organism levels. I examine the connection between steady-state membrane voltage (Vmem) and mitotic division, the relationship between mitochondrial membrane potential and aging, the role of epigenetic modifications in regulating gene expression, and the deliberate manipulation of bioelectric gradients to achieve desired outcomes in aging. This review emphasizes the need for further research to better comprehend the role of bioelectricity and chemical gradients in aging, and to identify potential targets for interventions to delay or alleviate the effects of aging.