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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Stress-sensitive nutrient consumption via steady and non-reversing dynamic shear in continuous-flow rotational bioreactors.
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Stress-sensitive nutrient consumption via steady and non-reversing dynamic shear in continuous-flow rotational bioreactors.

机译：通过在连续流旋转生物反应器中进行稳定和不可逆的动态剪切，对应力敏感的养分消耗。

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摘要

Stress-sensitive biological response is simulated in a modified parallel-disk viscometer that implements steady and unidirectional dynamic shear under physiological conditions. Anchorage-dependent mammalian cells adhere to a protein coating on the surface of the rotating plate, receiving nutrients and oxygen from an aqueous medium that flows radially and tangentially, accompanied by transverse diffusion in the z-direction toward the active surface. This process is modeled as radial convection and axial diffusion with angular symmetry in cylindrical coordinates. The reaction/diffusion boundary condition on the surface of the rotating plate includes position-dependent stress-sensitive nutrient consumption via the zr- and zTheta-elements of the velocity gradient tensor at the cell/aqueous-medium interface. Linear transport laws in chemically reactive systems that obey Curie's theorem predict the existence of cross-phenomena between scalar reaction rates and the magnitude of the second-rank velocity gradient tensor, selecting only those elements of nabla v experienced by anchorage-dependent cells that are bound to protein-active sites. Stress sensitivity via the formalism of irreversible thermodynamics introduces a zeroth-order contribution to heterogeneous reaction rates that must be quenched when nutrients, oxygen, chemically anchored cells, or vacant active protein sites are not present on the surface of the rotating plate. Computer simulations of nutrient consumption profiles via simple nth-order kinetics (i.e., n=1,2) suggest that rotational bioreactor designs should consider stress-sensitivity when the shear-rate-based Damkohler number (i.e., ratio of the stress-dependent zeroth-order rate of nutrient consumption relative to the rate of nutrient diffusion toward active cells adhered to the rotating plate) is greater than approximately 25% of the stress-free Damkohler number. Rotational bioreactor simulations are presented for simple 1st-order, simple 2nd-order, and complex stress-free kinetics, where the latter includes a 4th-order rate expression that considers adsorption/desorption equilibria via the Fowler-Guggenheim modification of the Langmuir isotherm for receptor-mediated cell-protein binding, accompanied by the formation of receptor complexes. Dimensionless parameters are identified to obtain equivalent stress-free nutrient consumption in the exit streams of 2-dimensional creeping-flow rotational bioreactors and 1-dimensional laminar-flow tubular bioreactors. Modulated rotation of the active plate at physiological frequencies mimics pulsatile cardiovascular flow and demonstrates that these rotational bioreactors must operate above the critical stress-sensitive Damkohler number, identified under steady shear conditions, before dynamic shear has a distinguishable effect on bioreactor performance.
机译：在改进的平行盘粘度计中模拟应力敏感的生物响应，该粘度计在生理条件下实现稳定和单向动态剪切。锚定依赖性哺乳动物细胞粘附在旋转板表面的蛋白质涂层上，从径向和切向流动的水性介质中吸收养分和氧气，并沿z方向朝着活动表面横向扩散。该过程被建模为在圆柱坐标系中具有对角对称的径向对流和轴向扩散。旋转板表面上的反应/扩散边界条件包括通过孔/水-介质界面处的速度梯度张量的zr和zTheta元素的位置相关的应力敏感养分消耗。服从居里定理的化学反应系统中的线性传输定律可预测标量反应速率和二等速度梯度张量的大小之间存在交叉现象，仅选择那些结合的锚定依赖性细胞经历的nabla v元素蛋白质活性位点。通过不可逆热力学的形式主义引起的应力敏感性为异质反应速率引入了零阶贡献，当营养成分，氧气，化学锚定的细胞或空置的活性蛋白位点不存在于旋转板的表面时，必须将其终止。通过简单的n阶动力学（即n = 1,2）对营养物消耗曲线的计算机模拟表明，当基于剪切速率的Damkohler数（即应力相关零位比）时，旋转生物反应器设计应考虑应力敏感性。养分消耗的有序速率相对于养分向附着在旋转板上的活性细胞扩散的养分速率大于无应力Damkohler数的约25％。给出了旋转生物反应器模拟，用于简单的一阶，简单的二阶和复杂的无应力动力学，其中后者包括一个四阶速率表达式，该表达式考虑了通过对Langmuir等温线进行Fowler-Guggenheim修正的吸附/解吸平衡。受体介导的细胞-蛋白质结合，伴随着受体复合物的形成。确定无量纲参数以获得二维蠕动旋转生物反应器和一维层流管状生物反应器的出口流中等效的无应力养分消耗。活动板在生理频率上的调制旋转模拟了脉动的心血管流动，并证明了这些旋转生物反应器必须在稳定剪切条件下确定的高于临界应力敏感的达姆霍勒数以上运行，然后动态剪切才能对生物反应器性能产生明显影响。

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