Structure-function relationship of biological gels revealed by multiple-particle tracking and differential interference contrast microscopy: The case of human lamin networks

Lamin [Formula presented] filaments organize into a thin dense meshwork underlying the nucleoplasmic side of the nuclear envelope. Recent experiments in vivo suggest that lamin [Formula presented] plays a key structural role in the nuclear envelope, but the intrinsic mechanical properties of lamin [Formula presented] networks remain unknown. To assess the potential mechanical contribution of lamin [Formula presented] in maintaining the integrity and providing structural support to the nucleus, we measured the micromechanical properties and examined the ultrastructural distribution of lamin [Formula presented] networks in vitro using particle tracking methods and differential interference contrast (DIC) microscopy. We exploit various surface chemistries of the probe microspheres (carboxylated, polyethylene glycol-coated, and amine-modified) to differentiate lamin-rich from lamin-poor regions and to rigorously extract local viscoelastic moduli from the mean-squared displacements of noninteracting particles. Our results show that human lamin [Formula presented] can, even in the absence of auxiliary proteins, form stiff and yet extremely porous networks that are well suited to provide structural strength to the nuclear lamina. Combining DIC microscopy and particle tracking allows us to relate directly the local organization of a material to its local mechanical properties, a general methodology that can be extended to living cells.