The Structural hallmarks of integrin activation are:
a) complete extension of the extracellular domains and
b) separation of the cytoplasmic leg domains (structural rearrangements detailed in [8, 9]).
This process facilitates integrin-mediated signaling, thus mechano-sensing and -transmitting. 

Integrin can be activated from two directions, from the inside by the regulated binding of proteins to the cytoplasmic tails, and from the outside by multivalent ligand binding. In either case, talin binding to the integrin β tails is an essential and the final common step ([10], reviewed in [11]). Though the two processes are conceptually separate, they are mutually cooperative i.e one can lead to the other. Some structural studies done with force application to mimic ligand/intracellular protein suggested that the combined action of these two events favor the transition from the closed, low affinity to a open, high affinity conformation of integrin [12]. Activation leads to bidirectional signaling crucial in a variety of anchorage-dependent events such as adhesion, cell spreading, migration, polarity and organization of the ECM leading to physiological changes (reviewed in [13]).

Here we discuss only well-established events that occur at the close proximity of integrin molecules localized on the plasma membrane. 

Ligand binding to external domain causes conformational changes that increase ligand affinity, modify protein-interaction sites in the cytoplasmic domains and thence the resulting signals. 

Besides conformational changes that extend integrin dimers ([29], reviewed in [13, 30]), multivalent ligand binding leads to clustering of integrins, which in turn activates Src family of kinases (SFKs) by autophosphorylation [31]. SFKs phosphorylate tyrosines of the integrin cytoplasmic domain (NPxY motifs) [32, 33] and other proteins [34, 35] leading to 
a) control of ligand binding strength 
b) alteration of binding with signaling molecules (kinases, GTPases and adaptors) [36], that constitute dynamic adhesion structures such as focal adhesions and podosomes (reviewed in [37, 38]). 

Upon alteration in the transmembrane and their proximal domains, the bent headpiece extends in less than 1 second [5] with intermediate affinity for ligands. Two models- “switchblade” and “deadbolt”- have been proposed for the mechanism of transmission of signals from across the plasma membrane leading to extension (reviewed in [1, 30]). 

According to the former model, leg separation causes a jackknife-like extension of the knee that releases the hybrid domain from the constraint of the bent form [8, 39]. The latter model postulates that the activated integrin remains in a bent state (even with bound ligand) until the interaction between the headpiece and the β-stalk is disrupted by piston-like movement of TM domains and sliding of the extracellular stalks [40]. 

Subsequent opening of the βA/hybrid domain hinge happens by spontaneous swing out of the hybrid domain and thus the integrin dimer becomes competent for ligand binding [9]. In immunologically relevant integrins, serine phosphorylation of integrin α subunit has also been shown as a critical criterion for αI conformation changes for ligand binding [41, 42]. 

Tension generated by the interplay of cytoskeletal forces and ECM stiffness has been shown to be sufficient for mechanical activation of integrins to aid cell motility [43]. Nevertheless, they are believed to constantly switch between ligand bound active and unbound inactive states, thus conferring the focal adhesions with distinct dynamics so as to endure rapid changes in force [44]. Also, bent integrins that move along the cell membrane may collide with other membrane proteins and this could result in structural changes [12]. However, further structural studies in physiologically relevant conditions are required to substantially establish this theory.