Abstract
Understanding force propagation through the fibrous extracellular matrix can elucidate how cells interact mechanically with their surrounding tissue. Presumably, due to elastic nonlinearities of the constituent filaments and their random connection topology, force propagation in fiber networks is quite complex, and the basic problem of force propagation in structurally heterogeneous networks remains unsolved. We report on a new technique to detect displacements through such networks in response to a localized force, using a fibrin hydrogel as an example. By studying the displacements of fibers surrounding a two-micron bead that is driven sinusoidally by optical tweezers, we develop maps of displacements in the network. Fiber movement is measured by fluorescence intensity fluctuations recorded by a laser scanning confocal microscope. We find that the Fourier magnitude of these intensity fluctuations at the drive frequency identifies fibers that are mechanically coupled to the driven bead. By examining the phase relation between the drive and the displacements, we show that the fiber displacements are, indeed, due to elastic couplings within the network. Both the Fourier magnitude and phase depend on the direction of the drive force, such that displacements typically propagate farther, but not exclusively, along the drive direction. This technique may be used to characterize the local mechanical response in 3-D tissue cultures, and to address fundamental questions about force propagation within fiber networks.
Highlights
The extracellular matrix (ECM) interacts with and provides a variety of mechanical and biochemical cues to cells [1,2]
We can improve identification of fibers which are mechanically coupled to the bead by taking into account the intensity fluctuations of all the pixels over each fiber
Fibers are visible in these I images as regions of increased I relative to the liquid regions that form the pores within the fibrin network
Summary
The extracellular matrix (ECM) interacts with and provides a variety of mechanical and biochemical cues to cells [1,2]. Experimental systems using naturally derived ECMs more closely mimic in vivo cell-ECM interactions than, for example, plastic [3]. Common naturally derived ECMs such as collagen and fibrin hydrogels exhibit important characteristics such as micron-scale pores and cell adhesion sites [4]. The fibrous nature of these ECMs plays potentially critical roles in cell-cell communication through the ECM, especially in 3-D culture systems [5,6]. Cells respond to forces an order-of-magnitude farther away in naturally derived fibrous materials than materials with sub-micron pores, often treated as a continuum at the cellular scale [7,8,9,10]. Understanding force propagation through naturally derived fibrous materials at the cellular scale is of great
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