Nuclear Envelope Permeability Barrier as a Fast‐Response Intracellular Mechanostat

• Published in: Advanced science Vol. 6; no. 21; pp. 1900709 - n/a
• Main Authors: Shahin, Victor, Kouzel, Ivan U., Rosso, Gonzalo, Liashkovich, Ivan
• Format: Journal Article
• Language: English
• Published: Weinheim John Wiley & Sons, Inc 01.11.2019; John Wiley and Sons Inc; Wiley
• Subjects: atomic force microscopy; Load; Mechanics; mechanobiology; Microscopy; nuclear envelope; Permeability; Physiology
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.201900709

The nuclear envelope is an undisputed component of the intracellular mechanotransduction cascades which collect, process, and respond to mechanical stimuli from the environment. At the same time, the nuclear envelope performs the function of a selective barrier between the nuclear and cytoplasmic compartments. Although the mechanosensing and the barrier functions of the nuclear envelope have both been subjects of intense research, a possible reciprocal relationship between them is only beginning to emerge. In this report, the role of the nucleocytoplasmic permeability barrier is evaluated in nuclear mechanics. Using a combination of atomic force and confocal microscopy, the functional state of the nucleocytoplasmic permeability barrier and the nuclear mechanics is monitored. By modulating the stringency of the barrier and simulating the active transport imbalance across the nuclear envelope, the decisive impact of these parameters on nuclear mechanics is demonstrated. It is concluded that the nucleocytoplasmic barrier is the second essential component of the intracellular mechanostat function performed by the nuclear envelope. A role of nucleocytoplasmic permeability barrier in nuclear mechanics is demonstrated by simultaneous confocal and atomic force microscopy. A compromised barrier results in a 2.4‐fold reduction of the nuclear elastic modulus and a diminished ability to withstand dynamic mechanical loads. Proposed ultrafiltration model of nuclear mechanics integrates the barrier function of the nuclear envelope with its role as an intracellular mechanostat.