Active and Passive Microrheology in Equilibrium and Nonequilibrium Systems

Abstract

Quantitatively measuring the mechanical properties of soft matter over a wide range of length and time scales, especially if a sample is as complex as typical biological materials, remains challenging. Living cells present a further complication because forces are generated within these nonequilibrium materials that can change material properties. We have here developed high-bandwidth techniques for active one-and two-particle microrheology to tackle these issues. By combining active micromanipulation of probe particles with an optical trap with high-resolution tracking of thermal motions of the very same particles by laser interferometry, we can both measure the mechanical properties of and, at the same time, identify nonequilibrium forces in soft materials. In both simple liquids and equilibrium cytoskeletal actin networks, active microrheology (AMR) proves to be less noise sensitive than and offers extended bandwidth (0.1-100 kHz) compared to passive microrheology (PMR), which merely tracks thermal motions. We confirm high-frequency power-law dynamics in equilibrium actin networks with two-particle AMR and also discuss low-frequency local mechanical response near probe particles which shows up in one-particle AMR. The combination of AMR and PMR allowed us to quantify nonthermal force fluctuations in actin networks driven by myosin motor proteins. Our approach offers a new direct way to investigate the nonequilibrium dynamics of living materials.

Active-passive calibration of optical tweezers in viscoelastic media

“…In the literature, previous investigations of probe particles manipulated by optical traps in viscoelastic media rely on ex situ calibration in a simple liquid such as water. 5,6 Here, we demonstrate calibration in situ in a viscoelastic medium.…”

Fibrin network adaptation to cell-generated forces

“…Spontaneous diffusive motions (thermal fluctuations) of 10 selected 1.0-μm beads, randomly embedded in fibrin and fibroblast-seeded fibrin networks, were measured per condition in the x and y direction at a fixed distance of 10 μm above the glass surface using customized LabVIEW software. The complex response function was determined by using the fluctuation-dissipation theorem to relate the bead motions to the thermal forces on the beads in the frequency domain (Mizuno et al 2008). The viscoelastic properties as a function of frequency were obtained from the complex response function via the generalized Stokes-Einstein relation (Gittes et al 1997;Mizuno et al 2008).…”

“…The complex response function was determined by using the fluctuation-dissipation theorem to relate the bead motions to the thermal forces on the beads in the frequency domain (Mizuno et al 2008). The viscoelastic properties as a function of frequency were obtained from the complex response function via the generalized Stokes-Einstein relation (Gittes et al 1997;Mizuno et al 2008). The data shown is the mean of five samples per condition calculated from a pool of 50 measurements of bead fluctuations, i.e., from 10 bead fluctuations per sample.…”

“…Rheology has two main techniques, i.e., microrheology and macrorheology. Microrheology has advantages over macrorheology such as much smaller sample volume, a high-frequency bandwidth (0 to 100 kHz), in situ measurement, and higher sensitivity to intracellular dynamics (Mizuno et al 2008;Tassieri et al 2012). Microrheology can be classified as passive microrheology, measuring spontaneous thermally driven fluctuations of beads, or active microrheology, driving the beads by an external force (oscillatory optical tweezers or magnetic tweezers (Jones et al 2015;Wessel et al 2015)).…”

Biomechanical Analysis of Infectious Biofilms

“…Microrheology: This methodology can be active or passive, and one or two particle [64]. For one particle, the motions of micron-scale particles undergoing passive Brownian motion are converted to G * (ω) or J * (ω) using thermodynamic relations [31,61,62], or they are actively driven via external forces and the moduli extracted directly [37,106].…”