You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.

Title: Symmetric exchange of multi-protein building blocks between stationary focal adhesions and the cytosol}
Article:
Abstract:
How can the integrin adhesome get self-assembled locally, rapidly, and correctly as diverse cell-matrix adhesion sites? Here, we investigate this question by exploring the cytosolic state of integrin-adhesome components and their dynamic exchange between adhesion sites and cytosol. Using fluorescence cross-correlation spectroscopy( FCCS) and fluorescence recovery after photobleaching( FRAP) we found that the integrin adhesome is extensively pre-assembled already in the cytosol as multi-protein building blocks for adhesion sites. Stationary focal adhesions release symmetrically the same types of protein complexes that they recruit, thereby keeping the cytosolic pool of building blocks spatiotemporally uniform. We conclude a model in which multi-protein building blocks enable rapid and modular self-assembly of adhesion sites and symmetric exchange of these building blocks preserves their specifications and thus the assembly logic of the system.
Introduction:
The integrin adhesome contains more than hundred proteins with multiple binding sites for each other( Zamir and Geiger, 2001; Zaidel-Bar et al., 2007; Byron et al., 2011; Kuo et al., 2011; Schiller et al., 2011; Geiger and Zaidel-Bar, 2012). Upon local signals, components of the integrin adhesome get self-assembled along the plasma membrane to form nascent adhesion sites and to further mature them to focal complexes and focal adhesions( Zamir and Geiger, 2001; Cukierman et al., 2002; Gardel et al., 2010; Zaidel-Bar and Geiger, 2010). These adhesion sites assemble, disassemble, and change their molecular content by exchanging their components with the surrounding cytosol( Wolfenson et al., 2011; Lavelin et al., 2013). Likewise, stationary adhesion sites are dynamically maintained by a balanced rapid exchange of constituents with the cytosol( Lele et al., 2008; Wolfenson et al., 2011; Lavelin et al., 2013). Considering the molecular diversity and complexity of cell-matrix adhesion sites( Zamir et al., 1999; Zamir and Geiger, 2001; Cukierman et al., 2002; Zamir et al., 2008), a major question is how can the integrin adhesome form these structures rapidly, locally, and correctly. In order to approach this question it is essential to consider and examine not only the adhesion sites themselves but also the state of their components in the cytosolic pool. However, the study of this fundamental aspect was largely abandoned so far, due to tacitly conceiving the cytosolic pool as a passive supply of individual integrin adhesome proteins. In this work we challenged this view by systematic FCCS and FRAP measurements. Strikingly, we found that the integrin adhesome is actually extensively pre-assembled already in the cytosol, forming multi-protein building blocks that can facilitate rapid and modular assembly of adhesion sites. The physical associations between adhesion site components are spatially uniform around stationary focal adhesions, indicating that these sites exchange their building blocks with the cytosol without altering them( i. e., symmetrically). Together, our results lead to a concept in which self-assembly of adhesion sites involves recruitment of multi-protein modules and symmetric exchange preserves the specifications of these building blocks in the cytosolic pool, thereby facilitating correct self-assembly.
Discussion:
We conclude that the integrin adhesome is extensively pre-assembled in the cytosol, thereby forming multi-protein building blocks for cell-matrix adhesion sites. Our results further indicate that these building blocks are size-confined( Figure 1) and are predominantly corresponding to the functional layers across focal adhesions of anchoring and integrin regulation, force transduction, and actin regulation( Figures 2 and 4). In the cytosol, the building blocks cannot form bigger structures due to dependencies between protein interactions. We propose that at the plasma membrane the system can get locally switched on to self-assemble adhesion sites by passing through checkpoints that induce additional protein interactions in the integrin adhesome( Figure 4). These checkpoints include mechanical stabilization of the active conformation of matrix-anchored integrin by actin polymerization( Puklin-Faucher and Sheetz, 2009; Vicente-Manzanares et al., 2009; Gardel et al., 2010; Shattil et al., 2010), activation of proteins( e. g., vinculin) at the plasma membrane by phosphatidyl-inositol-4-5-bisphosphate( PIP2)( Gilmore and Burridge, 1996; Zamir and Geiger, 2001), and mechanical stretching of proteins( e. g., talin and CAS) by actomyosin contractility( Riveline et al., 2001; Sawada et al., 2006; Johnson et al., 2007; del Rio et al., 2009; Puklin-Faucher and Sheetz, 2009; Gardel et al., 2010). Since adhesion sites are self-assembled structures, a standardized pool of building blocks is essential for their correct and efficient assembly. Symmetric material exchange between adhesion sites and cytosol satisfies this requirement by ensuring that building blocks will enter and exit adhesion sites without being altered. 10. 7554/eLife. 02257. 009Figure 4. A model of switchable formation of adhesion sites via pre-assembled multi-protein building blocks. The integrin adhesome is pre-assembled in the cytosol as multi-protein building blocks for adhesion sites. These building blocks are combinatorially diversified but confined in their size. Most of the building blocks form modules that are consistent with the previously reported( Kanchanawong et al., 2010) vertical continuum of anchoring, mechanosensing, and actin regulation layers across focal adhesions. In the cytosol, the pre-assembled building blocks cannot further assemble to form bigger structures due to mutual exclusiveness between protein interactions and allosteric regulations. On the plasma membrane, the system can get locally switched on to assemble an adhesion site by passing through checkpoints that enable additional protein interactions in the integrin adhesome. These checkpoints include anchoring of integrins to the extracellular matrix, mechanical stretching of proteins like talin and CAS by actomyosin contractility, and activation of proteins like vinculin and talin by PIP2 on the plasma membrane. Symmetric material exchange between adhesion sites and cytosol retains the wiring of the building blocks and therefore retains the assembly logic and switchability of the system. DOI: http://dx. doi. org/10. 7554/eLife. 02257. 009 Interestingly, in contrast to stationary focal adhesions, disassembling focal-adhesions might exchange material with the cytosol in an asymmetric manner. A previous study reported that in mouse embryonic fibroblasts FAK and vinculin associate with paxillin very close to disassembling focal adhesions but not far away from them( Digman et al., 2009). This study was based on a spatially resolved FCCS technique that gains spatial information on the expense of the sampling rate and integration time spent on each location, hence on the expense of the signal-to-noise ratio. This might underlie the difference from our results, which show the presence of FAK-paxillin and vinculin-paxillin associations far away from focal adhesions in REF52 and NIH3T3 cells. Yet, this study( Digman et al., 2009) importantly indicates a gradient in association strengths between these proteins emanating from disassembling focal adhesions, supporting in this case the asymmetric material exchange model. Asymmetric material exchange by disassembling focal adhesions can enable their rapid destruction by breaking them up to relatively bigger pieces, as well as be a mechanism by which they can affect other adhesion sites. The results presented here revise the concept about adhesion sites self-assembly, from a process that is mediated by the recruitment of individual proteins to a process involving pre-assembled multi-protein building blocks. This has implications for broad aspects of cell-matrix adhesion sites formation and regulation. Multi-protein building blocks, in comparison to single-protein building blocks, reduce the number of steps required for self-assembly of adhesion sites. With a properly designed regulation, such a reduction of steps can make the self-assembly of adhesion sites less sensitive to stochastic biochemical noise and therefore also faster. The regulation of adhesion sites assembly should cope with the combinatorial diversity of the building blocks. Since each protein can be a component of different building blocks, this regulation should consider each building block as a whole rather than its constituting proteins as individuals. Otherwise, the self-assembly process would lose control on the identity of the co-recruited proteins when recruiting a protein embedded in a multi-protein building block and thereby will be drifted to form aberrant structures. In order to understand such assembly logic of adhesion sites, it would be important to integrate interaction-dependencies across the integrin adhesome( Köster et al., 2012) and to comprehensively characterize the diversity of its high-order protein complexes in the cytosol by combining advanced optical and proteomic approaches( Heinze et al., 2004; Jain et al., 2011; Ridgeway et al., 2012).
The space between the cells in a multi-cellular organism is filled with a structure called the extracellular matrix . The roles of this matrix vary from tissue to tissue , and include providing the cell with structural support and signalling cues . Cells use large multi-protein structures along their plasma membrane , called cell-matrix adhesion sites , to attach to the extracellular matrix and sense its properties . These sites are rapidly self-assembled upon local cues and are dynamically maintained by exchanging their components with the cytosol of the cell . Given the large number of different proteins that can be used to build adhesion sites , and the large number of possible interactions between these proteins , a major question is—how are these structures self-assembled both rapidly and correctly ? Most research so far has concentrated on the adhesion sites themselves , as it has generally been assumed that their constituent proteins enter and leave these sites individually . However , using fluorescence techniques , Hoffmann et al . have now shown that these proteins are actually pre-assembled in the cytosol into small ‘building blocks’ . These can make the construction of cell-matrix adhesion sites quicker and more accurate by reducing the number of steps in the self-assembly process . In addition , under most circumstances , these building blocks do not change when they are exchanged between the cytosol and the adhesion site: this means that they can be re-used repeatedly and accurately . The work of Hoffmann et al . also raises questions about whether similar principles govern the self-assembly of other large intracellular multi-protein structures .