Objective: The objective of this mini-review is to exam- ine a subset of literature that demonstrates multiple inter- actions between mechanics and biology within the spine and propose how incorporation of these mechano-biologic interactions can be applied to improve the conceptual under- standing of tissue tolerances. Background: Low back pain represents a major mus- culoskeletal problem in the workplace. Traditional biome- chanical assessments have employed tissue tolerances as an approach for reducing workplace injuries; however, development of more universal biologically sensitive toler- ances requires incorporation of mechano-biologic interac- tions. Methods: A focused literature review addressing the interactions between mechanical loading and biology in the spine. Results: Mechanical loads applied to the body are distrib- uted across all spatial scales from the body to the tissues to the cells. These mechanical loads regulate cellular metabolism and over time can lead to tissue strengthening or weaken- ing. Mechanical loading also interacts with the biologic envi- ronment (e.g., tissue inflammation, nerve sensitization) to influence the perception of pain, thereby changing the risk of experiencing pain. Biologic tissues also exhibit time-dependent changes in mechanical behaviors that occur throughout the day and with disease, suggesting tissue tolerances are time dependent. Conclusion: Incorporating mechano-biologic interac- tions into the traditional tissue tolerance paradigm through describing tissue tolerances as a function of multiple factors (e.g., preexisting risk factors, underlying pathology, and time) may lead to the development of tissue tolerances that are more representative of the in vivo situation. Application: Efforts must work toward incorporat- ing biological concepts into tissue tolerances in order to improve risk assessment tools. Keywords: spine, low back, tissue loading, physiology, biomechanical models–spine, job risk assessment INTRODUCTION Chronic low back pain (LBP) is the leading cause of disability worldwide, with immense socioeconomic costs (>$100 billion in the United States alone) (Katz, 2006; Vos et al., 2012). In particular, disorders of the intervertebral disc (IVD) are commonly thought to contribute to the development of low back pain (Freemont, 2009; Freemont et al., 1997) and are the target tissue for a large proportion of clinical treat- ments. A primary goal of ergonomics research has been to prevent or control the occurrence of low back pain in the workplace. A traditional ergonomic paradigm compares the loads the tis- sue experiences to a reference load, or tissue tol- erance, which is the load limit above which an individual is at a greater risk of injury or pain. Although this ergonomic paradigm is a valuable tool, it does not incorporate the tissue’s biologic response to loading, which includes changes in structure with disease and the tissue’s ability to actively respond to its mechanical environment. Therefore, inclusion of the tissue’s dynamic biologic response to mechanical loading may enable the development of more universal tissue tolerances in living people. The objective of this mini-review is to highlight a subset of the lit- erature that demonstrates different interactions between mechanics and biology and suggest how incorporation of these interactions can be applied to improve the conceptual understand- ing of tissue tolerances and to prevent injury. THE PREMISE The spine functions through an intricate com- bination of biomechanical and biologic factors that interact in different spatial and temporal scales. A key concept underlying the interac- tion between mechanics and biology is that the cells within the tissue respond to a mechanical input and that this cellular output can modify the mechanical response of the tissue. When 657235HFS XX X 10.1177/0018720816657235Human FactorsBiologic Influences on Tissue Tolerances *Shared first authorship Address correspondence to William S. Marras, The Ohio State University, 1971 Neil Ave, Room 510, Columbus OH 43210, USA; e-mail: marras.1@osu.edu. The Contribution of Biomechanical-Biological Interactions of the Spine to Low Back Pain William S. Marras, * Benjamin A. Walter, * Devina Purmessur, Prasath Mageswaran, and Matthew G. Wiet, The Ohio State University, Columbus HUMAN FACTORS Vol. 58, No. 7, November 2016, pp. 965–975 DOI: 10.1177/0018720816657235 Copyright © 2016, Human Factors and Ergonomics Society. At the Forefront of HF/E