D A Hammer1, L A Tempelman, S M Apte
1School of Chemical Engineering, Cornell University, Ithaca, New York.
This study explores how cells stick to surfaces under the force of flowing fluid, a process important in immune responses and cancer spread. The researchers used computer simulations and an experimental model to test how cell adhesion behaves under shear stress. They found that the strength of adhesion depends on how much receptor-ligand bonds can stretch before breaking. A lower stretch rate means stronger adhesion. They also discovered that when cells have different numbers of receptors, their behavior under flow changes significantly. The experiments showed that not all cells roll slowly like neutrophils; instead, they either stick or don't interact at all. The study provides new insights into how adhesion mechanics affect cell behavior under flow and highlights the importance of receptor variability in physiological processes.
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Area of Science:
Background:
Understanding how cells adhere under fluid forces is essential for studying immune responses and cancer progression. Prior research has shown that neutrophils roll along blood vessel walls during inflammation, and cancer cells use similar adhesion mechanisms to spread. However, the relationship between receptor-ligand bond properties and cell behavior under shear flow remains unclear. This gap motivated the development of models that integrate mechanical and biological factors. Existing models often focus on individual cells, but population-level behavior is less explored. This paper introduces a new approach to simulate and test how cell adhesion varies under hydrodynamic conditions. The study addresses the need for a system that can measure adhesion dynamics in a controlled flow environment. It also aims to clarify how receptor number variability affects overall cell behavior. The research provides a framework for future investigations into how adhesion mechanics influence physiological processes.
Purpose Of The Study:
The fractional spring slippage of receptor-ligand bonds affects adhesion strength. Lower slippage means bonds can stretch without breaking quickly, leading to stronger adhesion.
A 25% standard deviation in receptor number leads to a significant increase in the average velocity of a cell population, even when the average receptor count is the same.
The model represents receptor-ligand bonds as springs and calculates cell motion from hydrodynamic, bonding, and colloidal forces to simulate adhesion under flow.
The model shows that not all cells roll slowly like neutrophils; instead, they exist in a binary state—either adherent or noninteracting—under hydrodynamic flow.
The goal of this research is to understand how cell adhesion behaves under hydrodynamic flow by combining simulations and experimental models. The study focuses on the interaction between cells and a ligand-coated surface under shear stress. The researchers aim to determine how receptor-ligand bond properties affect cell adhesion. They also seek to explore how variability in receptor numbers influences population-level adhesion. The motivation comes from the need to better model physiological processes like inflammation and metastasis. The study uses a microvilli-hard sphere model to simulate cell-surface interactions. It also develops an experimental system to validate the simulation results. The research addresses the lack of models that account for both mechanical and biological factors in adhesion under flow.
Main Methods:
The researchers used a microvilli-hard sphere model to simulate cell adhesion under shear flow. In this model, receptor-ligand bonds are represented as springs, and cell motion is determined by hydrodynamic, bonding, and colloidal forces. The simulation calculates the net force acting on a cell to predict its movement. They tested the model with parameters relevant to neutrophil rolling. The simulation was extended to model a population of cells with identical receptor numbers. They also simulated a heterogeneous population with a Gaussian distribution of receptor counts. The researchers developed an experimental system using RBL cells and polyacrylamide gels in a flow chamber. Cells were injected into a non-coated region and allowed to flow over an antigen-coated surface. They measured the spatial distribution of cell binding at different flow rates.
Main Results:
The simulations showed that the adhesive behavior of a cell depends on the fractional spring slippage of receptor-ligand bonds. A lower slippage means bonds can stretch without breaking quickly, leading to stronger adhesion. Homogeneous populations of cells with the same receptor count displayed a range of translational velocities. Heterogeneous populations with a 25% standard deviation in receptor number had significantly higher average velocities. The average receptor number was the same in both populations, but their velocities differed. The experimental results confirmed that not all cells roll slowly like neutrophils. Instead, cells appear to be in a binary state—either adherent or noninteracting. The study found that cell binding decreases as shear rate increases. These findings suggest that receptor number variability plays a key role in adhesion under flow.
Conclusions:
The study concludes that receptor-ligand bond properties strongly influence cell adhesion under hydrodynamic flow. The fractional spring slippage of bonds determines how much extension a bond can withstand before breaking. This affects whether a cell remains adherent or detaches. The simulations and experiments show that receptor number variability leads to differences in population-level adhesion. A 25% standard deviation in receptor count can significantly change the average velocity of a cell population. The experimental model supports the idea that cells exist in a binary state under flow—either adherent or noninteracting. This challenges the assumption that all cells roll similarly like neutrophils. The results suggest that adhesion under flow is more complex than previously thought. The study provides a framework for future research into how adhesion mechanics affect physiological processes.
The study found that cell binding decreases as shear rate increases, indicating that higher fluid forces reduce adhesion.
The findings suggest that receptor number variability and bond properties play a key role in adhesion under flow, challenging assumptions about uniform cell behavior.