Cell-Cell Adhesion

Cells are connected to each other through intercellular junctions. The mechanical properties of these junctions, which facilitate communication between cells, dictate their migration, growth, and proliferation. Likewise, deficiencies or mutations leading to abnormalities in cell junction behavior can result in skin lesions, heart arrhythmias, and tumor metastasis. Therefore, quantification of the mechanical interaction between cells may lead us to a deeper understanding of cell behavior, structure, communication, and therapeutics.

Figure 1. Composite representation of the MEMS-based method to characterize the mechanical behavior of individual cell-cell junctions. The device is designed to separate individual pairs of cells by applying precisely-controlled displacement and measuring the corresponding force. Cells are grown in patterned microwells (d), which interface the device through matching posts and holes (b & c) to facilitate their manipulation onto the devices The test is performed with simultaneous real-time confocal fluorescence imaging to observe the evolution of the cell-cell junctions under loading. Cells are shown here with their actin filaments stained red.


As a part of our investigation of biomechanics through single cell studies, we are developing MEMS-based techniques to probe the mechanical behavior of individual cell-cell junctions. A primary challenge in this research lies in achieving the range of forces and displacements required to accurately interrogate individual cell-cell junctions. Depending on the type of adhesion, the strength of a single junction ranges from 20 to 300 pN. Likewise, displacements required to significantly stimulate a junction can range from tens of nanometers up to microns. Accordingly, accurate characterization of the mechanical response of an individual cell-cell junction requires resolutions in force and displacement transduction of picoNewtons and nanometers respectively.

 

MEMS for Cell Mechanics  In this work, we leverage previous work from our MEMS-based in situ testing development to construct platforms (see Figure) simultaneously capable of:

  • Mechanical stimulation (force-displacement transduction) of the junctions between a pair of cells, and;
  • Real-time confocal fluorescence imaging of the evolution of cell-cell junctions.

MEMS lend themselves naturally to cellular and subcellular level mechanical testing. Due to their intermediate size, MEMS serve as an excellent interface between our naturally macroscale tools and micro- or nano-scale biological systems. The well-established MEMS literature details numerous sensors and actuators exhibiting excellent performance characteristics. The size and robustness of these devices creates the possibility of applying multiple independent sensors and actuators in cell-friendly environments. Furthermore, many of the MEMS-based sensing and actuation schemes scale favorably. For example, the time response, sensitivity, and power consumption of electrostatic displacement sensors improve as their dimensions shrink. Thus as devices are designed for finer scales, their performance improves. We apply these design principles to enable comprehensive characterization of cell-cell junction behavior not possible with conventional experimental techniques.

 

Personnel 

  • Horacio Espinosa (PI)
  • Allison Beese (postdoctoral fellow)
  • Krishanu Nandy (graduate student)

 

Collaborators 

  • Prof. Kathleen Green (Feinberg School of Medicine, Northwestern University)

 

Publications 

 

 

Robert R. McCormick School of Engineering and Applied Science
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