Eccentric muscle contractions: from single muscle fibre to whole muscle mechanics

Eccentric muscle loading encompasses several unique features compared to other types of contractions. These features include increased force, work, and performance at decreased oxygen consumption, reduced metabolic cost, improved energy efficiency, as well as decreased muscle activity. This review summarises explanatory approaches to long-standing questions in terms of muscular contraction dynamics and molecular and cellular mechanisms underlying eccentric muscle loading. Moreover, this article intends to underscore the functional link between sarcomeric components, emphasising the fundamental role of titin in skeletal muscle. The giant filament titin reveals versatile functions ranging from sarcomere organisation and maintenance, providing passive tension and elasticity, and operates as a mechanosensory and signalling platform. Structurally, titin consists of a viscoelastic spring segment that allows activation-dependent coupling to actin. This titin-actin interaction can explain linear force increases in active lengthening experiments in biological systems. A three-filament model of skeletal muscle force production (mediated by titin) is supposed to overcome significant deviations between experimental observations and predictions by the classic sliding-filament and cross-bridge theories. Taken together, this review intends to contribute to a more detailed understanding of overall muscle behaviour and force generation—from a microscopic sarcomere level to a macroscopic multi-joint muscle level—impacting muscle modelling, the understanding of muscle function, and disease.